Last update 18 Nov 2024

Buspirone Hydrochloride

Last update 18 Nov 2024

Overview

R&D Status

Clinical Result

Translational Medicine

Overview

Basic Info

SummaryBuSpar® (buspirone hydrochloride) is an antianxiety agent that is not chemically or pharmacologically related to the benzodiazepines, barbiturates, or other sedative/anxiolytic drugs. Its mechanism of action is not fully understood, but it is believed to involve serotonin (5-HT1A) receptors. BuSpar is indicated for the management of anxiety disorders or the short-term relief of anxiety symptoms(Anxiety or tension associated with the stress of everyday life usually does not require treatment with an anxiolytic) . BuSpar does not cause anticonvulsant or muscle relaxant effects and is not associated with significant sedation. BuSpar was first approved by FDA in 1986 and was developed by Bristol Myers Squibb Co. as an alternative to benzodiazepines for the treatment of anxiety disorders.

Drug Type

Small molecule drug

Synonyms

8-(4-(4-(2-Pyrimidinyl)-1-piperizinyl)butyl)-8-azaspiro(4,5)decane-7,9-dione, Buspirone, Buspirone hydrochloride (USP)

+ [13]

Target

5-HT1A receptor

Mechanism

5-HT1A receptor agonists(Serotonin 1a (5-HT1a) receptor agonists)

Therapeutic Areas

Other Diseases

Active Indication

Anxiety Disorders

Inactive Indication-

Originator Organization

Bristol Myers Squibb Co.

Active Organization

Cingulate Therapeutics LLC

PKU HealthCare Corp., Ltd.

Inactive Organization

Bristol Myers Squibb Co.

Drug Highest PhaseApproved

First Approval Date

US (29 Sep 1986),

Anxiety Disorders

Regulation-

Structure

Molecular FormulaC21H32ClN5O2

InChIKeyRICLFGYGYQXUFH-UHFFFAOYSA-N

CAS Registry33386-08-2

Clinical Trials associated with Buspirone Hydrochloride

NCT03432065 / WithdrawnPhase 2IIT

A Pilot Study of Buspirone for the Treatment of Anxiety in Youth with Autism Spectrum Disorders

The main objective of this exploratory 8-week pilot study is to evaluate the safety and efficacy of buspirone for the treatment of anxiety in youth (ages 6-17 years) with autism spectrum disorders. The study results will be used to generate hypotheses for a larger randomized-controlled trial with explicit hypotheses and sufficient statistical power.

Start Date01 Dec 2024

Sponsor / Collaborator

The General Hospital Corp.

IRCT20190624043991N28 / RecruitingPhase 3IIT

Investigating the effect of buspirone on irritative and obstructive symptoms in patients with bladder and bowel dysfunction (RCT); A double-blind randomized clinical trial study

Start Date25 Jul 2024

Sponsor / Collaborator

Tehran University of Medical Sciences

CTR20241607 / CompletedNot Applicable

盐酸丁螺环酮片人体生物等效性试验

[Translation] Bioequivalence study of buspirone hydrochloride tablets in human body

比较空腹和餐后给药条件下，山东京卫制药有限公司生产的盐酸丁螺环酮片（受试制剂，规格：10mg）与Teva Pharmaceuticals USA, Inc.持证的盐酸丁螺环酮片（参比制剂，规格：10mg）在中国健康人群中吸收程度和吸收速度的差异，并评价山东京卫制药有限公司生产的盐酸丁螺环酮片的安全性。

[Translation]

To compare the differences in the extent and rate of absorption of buspirone hydrochloride tablets (test preparation, strength: 10 mg) produced by Shandong Jingwei Pharmaceutical Co., Ltd. and buspirone hydrochloride tablets (reference preparation, strength: 10 mg) certified by Teva Pharmaceuticals USA, Inc. in healthy Chinese people under fasting and postprandial administration conditions, and to evaluate the safety of buspirone hydrochloride tablets produced by Shandong Jingwei Pharmaceutical Co., Ltd.

Start Date30 May 2024

Sponsor / Collaborator

Jewim Pharmaceutical (Shandong) Co., Ltd

100 Clinical Results associated with Buspirone Hydrochloride

100 Translational Medicine associated with Buspirone Hydrochloride

100 Patents (Medical) associated with Buspirone Hydrochloride

2,831

Literatures (Medical) associated with Buspirone Hydrochloride

01 Nov 2024·GENERAL HOSPITAL PSYCHIATRY

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

Article

Author: Wang, Fei ; Hu, ShuJia ; Na, WanQiu ; Xu, QiuXia ; Chen, Ke

BACKGROUND:

Late-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments.

OBJECTIVE:

This study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment.

METHODS:

A 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted.

RESULTS:

The ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue.

CONCLUSION:

The combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

01 Oct 2024·EXPERIMENTAL NEUROLOGY

N6-cyclohexyladenosine is better than meperidine and buspirone at suppressing metabolism during TTM32 but does not improve outcome after cardiac arrest

Article

Author: Jenkins, Mackenzie ; Chen, Chao-Yin ; Laughlin, Bernard W ; Drew, Kelly L ; Sugiura, M Hoshi

N⁶-clyclohexyladenosine (CHA) is an adenosine A₁ receptor agonist that inhibits thermogenesis. Cardiovascular side effects however, limit use of CHA as a therapeutic. We and others have shown that this can be reversed by administering 8-p-(sulfophenyl)theophylline (8-SPT), a nonspecific antagonist that does not cross the BBB. Other evidence shows that CNS actions of CHA may contribute to bradycardia through enhanced vagal tone and other mechanisms. Here we test the hypothesis that 8-SPT pretreatment alone is sufficient to prevent hypotension caused by CHA. To test this hypothesis, we pretreated rats with 8-SPT alone, and in combination with other antagonists to test the hypothesis that direct action of CHA on the heart is the primary mechanism by which CHA induces bradycardia and hypotension. Results show that pretreatment with 8-SPT alone is not sufficient to prevent CHA-induced hypotension. Pretreatment with 8-SPT or atropine alone did not prevent the fall in mean arterial pressure (MAP) and heart rate (HR), however, pretreatment with 8-SPT (25 mg/kg) and atropine (1 mg/kg) 15 min before CHA (1 mg/kg) preserves MAP and HR baseline values after CHA administration. We next asked if blood pressure was managed during the transition into a hypometabolic state, would prolong CHA-mediated inhibition of metabolism after cardiac arrest improve outcome better than anti-shivering medications meperidine and buspirone. We found that CHA-mediated hypotension can be mitigated by pretreatment with atropine and 8-SPT. This combination administered after cardiac arrest facilitated temperature management and metabolic suppression better than meperidine and buspirone, however, did not improve survival.

01 Oct 2024·Current pharmaceutical biotechnology

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride

Article

Author: Ullah, Hamid ; Lin, I-Ling ; Chiu, I-Hui ; Wu, Pao-Chu ; Fang, Chih-Wun ; Suhail, Muhammad ; Tsai, Ming-Jun

Background::

Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects.

Aim::

This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers.

Objective::

The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality.

Methods::

Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels.

Results::

FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone.

Conclusion::

The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

News (Medical) associated with Buspirone Hydrochloride

01 Apr 2024

·www.globenewswire.com

Cingulate Inc. Reports Fourth Quarter and Full Year 2023 Financial Results and Provides Clinical and Business Update

$17.8 Million Raised Since Beginning of 2023$9.1 Million of Debt Converted to Equity at a PremiumPhase 3 ADHD Data Continues to Impress KANSAS CITY, Kan., April 01, 2024 (GLOBE NEWSWIRE) -- Cingulate Inc. (NASDAQ: CING), a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, today announced its financial results for the twelve months ended December 31, 2023, and provided a clinical and business update. Highlights include capital raised from multiple sources and the addition of three independent board members. “I am pleased to report that Cingulate is stronger today than the end of last year,” said Shane J. Schaffer, Chairman and CEO of Cingulate Inc. “With the addition of three independent directors, each of whom possess deep experience in the pharmaceutical industry, small-cap publicly traded companies, and hold executive leadership roles within pharma, the Cingulate board is equipped to overcome the challenges ahead. “Our lead asset CTx-1301 continues to impress clinical investigators and key opinion leaders as we share our Phase 3 results. In addition, pharmaceutical companies in the U.S., Europe, and other territories have engaged in licensing discussions regarding their interest to commercialize our product. These tailwinds put Cingulate in a position to obtain non-dilutive capital and expand our pipeline of assets. “We are encouraged to see the capital markets improving as evidenced by our ability to raise more than $17 million dollars over the past year. Looking ahead, Cingulate has several financial instruments in place to raise additional capital while fighting to preserve shareholder’s equity. “Overall, I am very pleased with the progress made by our team in 2023 and into 2024. Our focus remains on executing our strategic plan and submitting CTx-1301 to the FDA.” CTx-1301 Data Exhibits Strong Effect Size On January 20, 2024, Cingulate presented results from the Phase 3 adult efficacy and safety study of its lead candidate, CTx-1301 (dexmethylphenidate), for the treatment of Attention Deficit / Hyperactivity Disorder (ADHD), at the 2024 American Professional Society of ADHD and Related Disorders (APSARD) conference in Orlando, FL. The results were previously presented at the 36th Annual Psych Congress in September 2023, where the data was selected as a finalist for the Psych Congress’s First Annual Poster Awards. The Cingulate poster presented at APSARD provided additional insight regarding CTx-1301’s impressive effect size. Effect size conveys clinical significance rather than statistical significance, is not reliant on sample size, and allows for comparison across trials. The poster presented may be viewed here. The study was not intended nor did it achieve statistical significance on the primary endpoint but demonstrated a trend towards significance despite its modest sample size in improving ADHD symptoms with a rapid onset of action and entire active-day duration. Cingulate Receives Guidance from FDA on Path Forward for Anxiety Asset CTx-2103 (buspirone) In December 2023, Cingulate received input from the FDA regarding the regulatory pathway for CTx-2103, and the design of clinical studies for filing of an IND. Based on this FDA feedback, we believe that we can seek and win approval of CTx-2103 under the 505(b)(2) pathway, which typically requires less time and resources than the 505(b)(1) full NDA pathway. $10.7 Million of Capital Raised and $3.3 Million of Debt Converted to Equity in 2024 Since January 1, 2024, the Company sold shares of common stock under its At the Market Offering Agreement with H.C. Wainwright & Co., LLC for gross proceeds of $3.2 million. In February 2024, the Company closed a $7.5 million public offering of its common stock (or pre-funded warrants in lieu thereof) and Series A and Series B warrants to purchase shares of common stock, at a public offering price of $2.00 per share (or common stock equivalent in lieu thereof) and accompanying warrants. Additionally, in January 2024, Werth Family Investment Associates, LLC (WFIA), the manager of which is Peter J. Werth, a member of the Cingulate board of directors, converted at a 10 percent premium to market the remaining $3.3 million of outstanding debt plus accrued interest into pre-funded warrants to purchase shares of common stock. $7.1 Million of Capital Raised and $5.8 Million of Debt Converted to Equity in 2023 In September 2023, Cingulate closed a $4.0 million public offering of shares of common stock (or common stock equivalents in lieu thereof) and Series A and Series B warrants to purchase shares of common stock, at public offering price of $11.55 per share (or common stock equivalent in lieu thereof) and accompanying warrants. In addition, during 2023, Cingulate sold shares of common stock through its ATM Agreement and its Purchase Agreement with Lincoln Park Capital Fund, LLC for aggregate gross proceeds of $2.1 million. Finally, in August 2023, WFIA purchased shares of common stock for $1.0 million through a private placement priced at the market and, in September 2023, WFIA converted at a 47% premium to market $5.8 million of outstanding debt and accrued interest into pre-funded warrants to purchase shares of common stock. Jennifer Callahan Promoted to CFO In January 2024, Cingulate promoted longtime Controller Jennifer Callahan to Chief Financial Officer, succeeding Lou Van Horn, who retired from the company in December 2023. Three Independent Directors Appointed to Cingulate Board In February 2024, Cingulate appointed three independent directors to its board: Jay Roberts, Bryan Lawrence, and Jeff Ervin. Please visit Cingulate.com for more information about the new directors. Fourth Quarter and Full Year Results Cash Position: As of December 31, 2023, Cingulate had $52,416 in cash and cash equivalents. Additionally, we have raised $10.7 million from the sale of securities in 2024 to date and we believe that our cash will satisfy our capital needs through late in the second quarter of 2024 under our current business plan. Management continues to evaluate additional strategies to obtain funding, which may include additional equity offerings, issuance of debt, or other capital sources, including potential collaborations with other companies or other strategic transactions. R&D Expenses: Research and development expenses were $5.0 million for the three months ended December 31, 2023, compared to $1.9 million for the same period in 2022. Research and development expenses were $15.5 million for the year ended December 31, 2023, compared to $9.0 million for the year ended December 31, 2022. These increases were primarily the result of increased clinical activity in 2023 as compared to 2022. During the third quarter of 2023, we initiated two Phase 3 studies for CTx-1301, the pediatric dose optimization onset and duration study and the fixed dose pediatric and adolescent safety and efficacy study. In addition, the Phase 3 adult dose-optimization study for CTx-1301 was completed in June 2023. Manufacturing for these Phase 3 studies also occurred during 2023. G&A Expenses: General and administrative expenses were $1.8 million for the three months ended December 31, 2023, compared to $2.5 million for the same period in 2022. General and administrative expenses were $7.3 million for the year ended December 31, 2023, compared to $8.5 million for the year ended December 31, 2022. These decreases were primarily the result of a decrease in our directors’ and officers’ insurance premium from 2022 to 2023. The decrease in directors’ and officers’ insurance premium was offset by increases in certain professional fees primarily the result of the timing of services performed relating to our annual audit. Net Loss: Net loss was $6.9 million for the three months ended December 31, 2023, compared to $4.6 million for the same period in 2022. Net loss was $23.5 million for the year ended December 31, 2023, compared to $17.7 million for the year ended December 31, 2022. The increase in the net loss from 2022 to 2023 primarily relates to a significant increase in development activity as described above. Cingulate Inc.Consolidated Balance Sheet Data December 31, December 31, 2023 2022 Cash and cash equivalents$52,416 $5,356,276 Total assets$3,491,436 $11,405,057 Total liabilities$10,360,865 $7,523,035 Accumulated deficit$(92,943,443) $(69,408,496)Total stockholders' equity$(6,869,429) $3,882,022 Cingulate Inc.Consolidated Statements of Operations Three Months Ended December 31, Year Ended December 31, 2023 2022 2023 2022 Operating expenses: Research and development$4,984,909 $1,931,654 $15,493,304 $8,995,280 General and administrative 1,812,242 2,543,371 7,265,885 8,506,438 Operating loss (6,797,151) (4,475,025) (22,759,189) (17,501,718) Interest and other income (expense), net (137,546) (130,002) (775,758) (174,514)Loss before income taxes (6,934,697) (4,605,027) (23,534,947) (17,676,232)Income tax benefit (expense) - - - - Net loss$ (6,934,697) $ (4,605,027) $ (23,534,947) $ (17,676,232) About Cingulate®Cingulate Inc. is a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, designed to improve the lives of patients suffering from frequently diagnosed conditions characterized by burdensome daily dosing regimens and suboptimal treatment outcomes. With an initial focus on the treatment of Attention Deficit/Hyperactivity Disorder (ADHD), Cingulate is identifying and evaluating additional therapeutic areas where its PTR technology may be employed to develop future product candidates, such as anxiety disorders. Cingulate is headquartered in Kansas City, KS. For more information visit Cingulate.com. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include all statements, other than statements of historical fact, regarding our current views and assumptions with respect to future events regarding our business, including statements with respect to our plans, assumptions, expectations, beliefs and objectives with respect to product development, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. These statements are generally identified by the use of such words as “may,” “could,” “should,” “would,” “believe,” “anticipate,” “forecast,” “estimate,” “expect,” “intend,” “plan,” “continue,” “outlook,” “will,” “potential” and similar statements of a future or forward-looking nature. Readers are cautioned that any forward-looking information provided by us or on our behalf is not a guarantee of future performance. Actual results may differ materially from those contained in these forward-looking statements as a result of various factors disclosed in our filings with the Securities and Exchange Commission (SEC), including the “Risk Factors” section of our Annual Report on Form 10-K filed with the SEC on March 10, 2023. All forward-looking statements speak only as of the date on which they are made, and we undertake no duty to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. Investor & Public Relations:Thomas DaltonVice President, Investor & Public Relations, Cingulatetdalton@cingulate.com(913) 942-2301 Matt KrepsDarrow Associatesmkreps@darrowir.com(214) 597-8200

Financial StatementExecutive ChangePhase 3

06 Mar 2024

·www.globenewswire.com

Cingulate to Attend DCAT Week 2024 in New York City

Will Host Licensing Meetings with Multiple Parties to Discuss Assets, Pipeline and TechnologyKANSAS CITY, Kan., March 06, 2024 (GLOBE NEWSWIRE) -- Cingulate Inc. (NASDAQ: CING), a biopharmaceutical company utilizing its proprietary Precision Timed Release™ (PTR™) drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, announced today that it will be attending DCAT Week (Drug, Chemical & Associated Technologies Association) March 18-21, 2024, in Midtown Manhattan. Cingulate Chairman and CEO Shane J. Schaffer, and Cingulate COO Laurie A. Myers, will be joined at the DCAT by Global PharmaPartners, INC. (also known worldwide as “GPP”) to host meetings regarding Cingulate’s pipeline and product portfolio, including its lead Phase 3 candidate CTx-1301 (dexmethylphenidate) for the treatment of attention deficit/hyperactivity disorder (ADHD), and CTx-2103 (buspirone) for the treatment of anxiety. “Cingulate is excited to be attending DCAT this year with Global PharmaPartners, Inc. to seek out business partnerships with excellent co-development/commercial parties, and we believe it’s an excellent venue to discuss our leading assets, pipeline, and disruptive drug delivery platform technology,” Schaffer said. What: DCAT Week 2024 Where: Omni Berkshire Place Hotel: 21 E 52nd St Madison Ave, New York City, NY 10022-5389 When: March 18-21, 2024 Contact: To arrange meetings with Cingulate leadership please contact Jonathan Camerer with Global PharmaPartners (GPP): 417-576-5082 jonathancamerer@globalpharmapartners.com About Attention Deficit/Hyperactivity Disorder (ADHD)ADHD is a chronic neurobiological and developmental disorder that affects millions of children and often continues into adulthood. The condition is marked by an ongoing pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. In the U.S., approximately 6.4 million children and adolescents (11 percent) aged under the age of 18 have been diagnosed with ADHD. Among this group, approximately 80 percent receive treatment, with 65-90 percent demonstrating clinical ADHD symptoms that persist into adulthood. Adult ADHD prevalence is estimated at approximately 11 million patients (4.4 percent), almost double the size of the child and adolescent segment combined. However, only an estimated 20 percent receive treatment. About CTx-1301Cingulate’s lead candidate, CTx-1301, utilizes Cingulate’s proprietary PTR drug delivery platform to create a breakthrough, multi-core formulation of the active pharmaceutical ingredient dexmethylphenidate, a compound approved by the FDA for the treatment of ADHD. Dexmethylphenidate is part of the stimulant class of medicines and increases norepinephrine and dopamine activity in the brain to affect attention and behavior. While stimulants are the gold standard of ADHD treatment due to their efficacy and safety, the long-standing challenge continues to be providing patients with an entire active-day duration of action. CTx-1301 is designed to precisely deliver three releases of medication at the predefined time, ratio, and style of release to optimize patient care in one tablet. The result is a rapid onset and entire active-day efficacy, with the third dose being released around the time when other extended-release stimulant products begin to wear off. About AnxietyAnxiety disorders are the most common mental health concern in the U.S.1 Anxiety is the feeling of fear that occurs when faced with threatening or stressful situations or can be endogenous and not have an identified stressor. It can be a normal response when confronted with danger, but, if severe and chronic and affects functioning, it could be regarded as an anxiety disorder. An estimated 31 percent of U.S. adults experience an anxiety disorder at some time in their lives.2 People may live with anxiety for years before they are diagnosed or treated. The global COVID-19 crisis has exacerbated the diagnosis and treatment of anxiety and anxiety related disorders and as a result is a priority within the class of unmet medical needs in mental health. About CTx-2103 CTx-2103 is a novel, trimodal, extended-release tablet of buspirone that incorporates Cingulate’s proprietary PTR™ drug delivery platform. CTx-2103 is being studied for the treatment of anxiety and/or anxiety-related disorders. Buspirone, an azapirone derivative and a 5-HT1A partial agonist, was the first non-benzodiazepine anxiolytic introduced for the treatment of generalized anxiety disorder. Buspirone may exhibit a decreased side-effect profile compared to other anxiolytic treatments. Unlike benzodiazepines and barbiturates, there is no associated risk of physical dependence or withdrawal with buspirone use due to the lack of effects on gamma-aminobutyric acid receptors. About Precision Timed Release™ (PTR™) Platform TechnologyCingulate is developing ADHD and anxiety disorder product candidates capable of achieving true once-daily dosing using Cingulate’s innovative PTR drug delivery platform technology. It incorporates a proprietary Erosion Barrier Layer (EBL) providing control of drug release at precise, pre-defined times with no release of drug prior to the intended release. The EBL technology is enrobed around a drug-containing core to give a tablet-in-tablet dose form. It is designed to erode at a controlled rate until eventually the drug is released from the core tablet. The EBL formulation, Oralogik™, is licensed from BDD Pharma. Cingulate intends to utilize its PTR technology to expand and augment its clinical-stage pipeline by identifying and developing additional product candidates in other therapeutic areas in addition to Anxiety and ADHD where one or more active pharmaceutical ingredients need to be delivered several times a day at specific, predefined time intervals and released in a manner that would offer significant improvement over existing therapies. To see Cingulate’s PTR Platform, click here. About Cingulate Inc.Cingulate Inc. (NASDAQ: CING), is a biopharmaceutical company utilizing its proprietary PTR drug delivery platform technology to build and advance a pipeline of next-generation pharmaceutical products, designed to improve the lives of patients suffering from frequently diagnosed conditions characterized by burdensome daily dosing regimens and suboptimal treatment outcomes. With an initial focus on the treatment of ADHD, Cingulate is identifying and evaluating additional therapeutic areas where PTR technology may be employed to develop future product candidates, including to treat anxiety disorders. Cingulate is headquartered in Kansas City. For more information, visit Cingulate.com. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include all statements, other than statements of historical fact, regarding our current views and assumptions with respect to future events regarding our business, including statements with respect to our plans, assumptions, expectations, beliefs and objectives with respect to product development, clinical studies, clinical and regulatory timelines, market opportunity, competitive position, business strategies, potential growth opportunities and other statements that are predictive in nature. These statements are generally identified by the use of such words as “may,” “could,” “should,” “would,” “believe,” “anticipate,” “forecast,” “estimate,” “expect,” “intend,” “plan,” “continue,” “outlook,” “will,” “potential” and similar statements of a future or forward-looking nature. Readers are cautioned that any forward-looking information provided by us or on our behalf is not a guarantee of future performance. Actual results may differ materially from those contained in these forward-looking statements as a result of various factors disclosed in our filings with the Securities and Exchange Commission (SEC), including the “Risk Factors” section of our Annual Report on Form 10-K filed with the SEC on March 10, 2023. All forward-looking statements speak only as of the date on which they are made, and we undertake no duty to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except to the extent required by law. Investor & Public Relations:Thomas DaltonVice President, Investor & Public Relations, Cingulatetdalton@cingulate.com(913) 942-2301Matt KrepsDarrow Associatesmkreps@darrowir.com(214) 597-8200

Phase 3License out/inDrug Approval

21 Feb 2024

·www.biospace.com

Enveric Biosciences Unveils Library of Preclinical Compounds Across Multiple Distinct Molecule Classes Targeting Mental Health Disorders

Novel compounds protected under Enveric’s intellectual property portfolio provide potential licensing opportunities and non-dilutive revenue streams. CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Enveric Biosciences (NASDAQ: ENVB) (“Enveric” or the “Company”), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders, today announced the discovery of multiple, promising novel compounds sourced using the company’s Psybrary™ platform and proprietary computational chemistry and artificial intelligence (AI) drug-discovery system (PsyAI™). The novel compounds span seven distinct molecule classes totaling at least 57 unique product opportunities, all of which are protected by Enveric’s expansive intellectual property portfolio and represent potential out-licensing opportunities and non-dilutive revenue streams for the Company. Together, the novel and distinct molecule classes broaden and deepen Enveric’s library of assets targeting difficult-to-address mental health disorders, adding to its lead candidate EB-003, a first-in-class neuroplastogen designed to eliminate hallucinations, and EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin. “Our ability to identify EB-003 and EB-002 as our lead drug candidates was the result of an extensive process in which our research team analyzed more than one thousand compounds spanning numerous classes of molecules, utilizing our proprietary PsyAI and Psybrary platforms,” said Joseph Tucker, Ph.D., Director and CEO of Enveric. “As a result, Enveric now possesses what we believe to be one of the most diverse portfolios of potential drug molecules for the treatment of key, underserved mental health and neurological disorders. Our dedicated approach to protecting our discoveries should enable us to generate significant near- and long-term value for our shareholders via potential partnering and/or licensing agreements.” The novel compounds span seven diverse molecule classes and subclasses, including: Novel Serotonin-Norepinephrine-Dopamine Reuptake Inhibitors (SNDRI) Also known as triple reuptake inhibitors (TRIs), SNDRIs are an emerging class of medications designed to treat severe depression and anxiety disorders. Enveric SNDRI compounds show strong binding to serotonin transporter (SERT), norepinephrine transporter (NET) and dopamine transporter (DAT). Enveric SNDRI compounds also demonstrate distinct additional serotonin receptor binding profiles that bear similarities to those of the antidepressant Nefazodone and the anxiolytic Buspirone. Non-selective Serotonin Reuptake Inhibitor (NSRI) Enveric NSRI compounds show strong binding to SERT, as well as to the 5-HT1A receptor, known to be a therapeutically valuable target. Certain of Enveric’s NSRIs demonstrate additional binding to various serotonin and dopamine family receptors, with binding profiles similar to the antidepressant Vortioxetine and the atypical antipsychotic Aripiprazole. Novel MDMA Derivatives (EMD) Series Twenty novel MDMA derivatives are separated into three subgroups: Strong 5-HT2A receptor binding, Weak 5-HT2A binding, and No 5-HT2A receptor binding. Current literature indicates agonism of the 5-HT2A receptor is linked to hallucination in humans and also to the induction of neuroplasticity. Each subgroup of Enveric’s novel MDMA derivatives demonstrates unique and expanded receptor binding activity targeting adrenergic and/or dopaminergic receptors as well as epinephrine/norepinephrine family receptors. Some of the resulting receptor binding profiles are similar to the anxiolytic Buspirone, the antiepileptic Fenfluramine, the ADHD drug Guanfacine, and the atypical antipsychotic Aripiprazole. Bifunctional Psilocin Prodrugs (BPP) BPPs are readily absorbed, detectable in plasma, and converted to therapeutically relevant levels of plasma psilocin, with demonstrated lower Head Twitch Response (HTR) relative to psilocybin in mice; HTR is reported in the literature to be a predictive indicator for hallucination in humans. Each BPP parent prodrug demonstrates its own unique binding pro serotonin 5-HT1A receptor, 5-HT1B receptor and SERT, with similarities to anxiolytics Buspirone, antidepressant/anxiolytic Flesinoxan, and the antidepressant Paroxetine. Novel Psilocin Prodrug (NPP) Series NPPs are designed to be metabolized to release therapeutic levels of systemic psilocin at varying rates, providing treatment regimen optionality. Included in this series are four compounds that can be converted upon direct intravenous injection to psilocin: potentially bypassing the need for first-pass metabolism, making them amenable to non-oral forms of administration (e.g. intranasal, sublingual, buccal). Melatonin-Receptor Agonist (MRA) Series Melatonin, a natural indolamine, is essential for regulating circadian rhythm in mammals and is often used in to treat a variety of sleep disorders. Enveric MRA compounds demonstrate strong binding to the MT1 Melatonin receptor with some being highly selective for MT1 while others demonstrate expanded target binding profiles similar to the antidepressants Agomelatine, Vortioxetine, Imipramine, and Trazodone. Neuroplastogenic Antidepressant (NAD-01) Designed to induce neuroplasticity and promote long-term therapeutic benefit in patients suffering from severe depressive mood disorders. Demonstrates neuroplastogenic activity comparable to known 5-HT2A receptor agonist N,N-Dimethyltryptamine (DMT). Demonstrates weak 5-HT2A receptor binding affinity and activation. Produces lower Head Twitch Response relative to psilocin and DMT, while promoting recovery of sucrose preference (SP) in stressed mice - an accepted model for evaluation of antidepressant activity. For more information about Enveric’s novel preclinical compounds spanning multiple, distinct classes of molecules, please visit: . About Enveric Biosciences Enveric Biosciences (NASDAQ: ENVB) is a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of depression, anxiety, and addiction disorders. Leveraging its unique discovery and development platform, Psybrary™, Enveric has created a robust intellectual property portfolio of New Chemical Entities for specific mental health indications. Enveric’s lead program, EB-003, is a first-in-class approach to the treatment of difficult-to-address mental health disorders designed to promote neuroplasticity without inducing hallucinations in the patient. Enveric is also developing EB-002, formerly EB-373, a next generation synthetic prodrug of the active metabolite, psilocin, being studied as a treatment of psychiatric disorders. Enveric is headquartered in Naples, FL with offices in Cambridge, MA and Calgary, AB Canada. For more information, please visit . Forward-Looking Statements This press release contains forward-looking statements and forward-looking information within the meaning of applicable securities laws. These statements relate to future events or future performance. All statements other than statements of historical fact may be forward-looking statements or information. Generally, forward-looking statements and information may be identified by the use of forward-looking terminology such as “plans,” “expects” or “does not expect,” “proposed,” “is expected,” “budgets,” “scheduled,” “estimates,” “forecasts,” “intends,” “anticipates” or “does not anticipate,” or “believes,” or variations of such words and phrases, or by the use of words or phrases which state that certain actions, events or results may, could, should, would, or might occur or be achieved. Forward-looking statements may include historical statements and statements regarding beliefs, plans, expectations, or intentions regarding the future and are based on the beliefs of management as well as assumptions made by and information currently available to management. Actual results could differ materially from those contemplated by the forward-looking statements as a result of certain factors, including, but not limited to, the ability of Enveric to: carry out successful clinical programs in Australia; achieve the value creation contemplated by technical developments; avoid delays in planned clinical trials; establish that potential products are efficacious or safe in preclinical or clinical trials; establish or maintain collaborations for the development of therapeutic candidates; obtain appropriate or necessary governmental approvals to market potential products; obtain future funding for product development and working capital on commercially reasonable terms; scale-up manufacture of product candidates; respond to changes in the size and nature of competitors; hire and retain key executives and scientists; secure and enforce legal rights related to Enveric’s products, including patent protection; identify and pursue alternative routes to capture value from its research and development pipeline assets; continue as a going concern; and manage its future growth effectively. A discussion of these and other factors, including risks and uncertainties with respect to Enveric, is set forth in Enveric’s filings with the Securities and Exchange Commission, including Enveric’s Annual Report on Form 10-K and its Quarterly Reports on Form 10-Q. Enveric disclaims any intention or obligation to revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

License out/in

100 Deals associated with Buspirone Hydrochloride

External Link

KEGG	Wiki	ATC	Drug Bank
D00702	Buspirone Hydrochloride	N05BE01	DB00490

R&D Status

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Anxiety Disorders	US	Bristol Myers Squibb Co.	29 Sep 1986

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04807517 (CTgov)	Phase 4	Performance Anxiety \| Williams Syndrome	20	buspirone	zjzzkgehfa(ssbfqvdtxr) = bajmlficqc sdlgqqwstn (awjnomlmlq, iiqfstwkji - luammsexcu) View more	-	19 Sep 2024
NCT03587142 (BESST, CTgov)	Phase 2	Gastroparesis \| Feeding and Eating Disorders	96	Buspirone (Buspirone)	qytknyqynv(presdvgtch) = xvxslwjzeb baefqauekk (sjutuupide, xlpbbuepmn - etywjdwlnf) View more	-	15 Jun 2023
				Placebo (Placebo)	qytknyqynv(presdvgtch) = wqdvrzdiyv baefqauekk (sjutuupide, dbzaimvvdi - iqfvsnfnhf) View more
ARVO2021	Not Applicable	stress oxidative	-	Buspirone	snuagwtfnf(eiyogzaodk) = nokamwcywl ojftrbynlv (jwdqwsokkh, 8.009)	-	01 Jun 2021
				Vehicle	snuagwtfnf(eiyogzaodk) = xkonihffnz ojftrbynlv (jwdqwsokkh, 3.861)
NCT03538431 (CTgov)	Phase 4	Autism Spectrum Disorder	26	Buspirone (Buspirone)	hvzbgypzmp(dzebqgdwbg) = kkrelxpucx ztzjyjxrto (txnzrzqcru, yxynmykyip - kvrxpnkuxu) View more	-	18 Mar 2021
				Buspirone (Unmedicated)	hvzbgypzmp(dzebqgdwbg) = vjkisfaeom ztzjyjxrto (txnzrzqcru, vjpwuroqdt - ygimozzqnc) View more
Pubmed \| Am J Gastroenterol	Not Applicable	Abdominal Pain	117	Buspirone	(rwhcztbwni) = ccpueclwat dkkctzbsen (bplkymbedj )	-	01 May 2020
				Placebo	(rwhcztbwni) = ghuxtuycnl dkkctzbsen (bplkymbedj )
AAN2020	Not Applicable	Abdominal Pain	117	Buspirone	sddbaukjlw(swvodahfqq) = pxxkpwxira oodhjxqgyf (fhuzqifzqg )	Negative	14 Apr 2020
				Placebo	sddbaukjlw(swvodahfqq) = awfqlmiebw oodhjxqgyf (fhuzqifzqg )
NCT02458469 (REST-SCI, CTgov)	Phase 2	Spinal Cord Injuries \| Sleep Apnea, Central	15	buspirone (Buspirone)	cagkubzfog(qkvbydtcdq) = glhskuepeu jsorafjcjz (nsjtgwwsea, aqptdypezv - zbqkghkaez) View more	-	09 Apr 2020
				Trazodone (Trazodone)	cagkubzfog(qkvbydtcdq) = ijsrxyuucm jsorafjcjz (nsjtgwwsea, rldyuagkoa - mqkfwhlnvu) View more
NCT02803749 (CTgov)	Phase 2	Anxiety Disorders \| Parkinson Disease	21	Buspirone (Buspirone)	vewkvaqned(ymeoguydlm) = nnsgrotjtz gztzziesec (fjnrebbtbe, xpejslazon - aoeclljrzz) View more	-	02 Jan 2020
				Placebo (Placebo)	vewkvaqned(ymeoguydlm) = fnercfxocc gztzziesec (fjnrebbtbe, lvkisjfaof - qtebaeqpvn) View more
ESC2019	Not Applicable	Heart Failure	16	Buspirone	nrdsxiamnm(mjyvikchcg) = pwmhbjtpsv hmweskzwkb (gzttfzqfkx ) View more	-	02 Sep 2019
				Placebo	nrdsxiamnm(mjyvikchcg) = hzedtjfete hmweskzwkb (gzttfzqfkx ) View more
ESC2019	Not Applicable	Heart Failure	16	Buspirone	ogblizblaj(aqnfqhsmzg) = jbgkfsclcs feydftetho (adkabzgsvz, 2.3 - 11.5) View more	-	28 May 2019
				Placebo	ogblizblaj(aqnfqhsmzg) = qldvvlivpi feydftetho (adkabzgsvz, 6.3 - 18.8) View more

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis