Delving into the Latest Updates on Vabicaserin Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Vabicaserin, Vabicaserin hydrochloride (USAN), 戊卡色林

+ [4]

Target

5-HT2C receptor

Mechanism

5-HT2C receptor agonists(Serotonin 2c (5-HT2c) receptor agonists)

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Schizophrenia

Originator Organization

Pfizer Inc.

Active Organization-

Inactive Organization

Ayerst-Wyeth Pharmaceuticals, Inc.Wyeth AB

Pfizer Inc.

+ [2]

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC15H21ClN2

InChIKeyPYPPENBDXAWXJC-QNTKWALQSA-N

CAS Registry887258-94-8

Introduction Conventional antipsychotic drugs that attenuate dopaminergic neural transmission are ineffective in approximately one-third of patients with schizophrenia. This necessitates the development of non-dopaminergic agents. Methods A systematic search was conducted for completed phase II and III trials of compounds for schizophrenia treatment using the US Clinical Trials Registry and the EU Clinical Trials Register. Compounds demonstrating significant superiority over placebo in the primary outcome measure in the latest phase II and III trials were identified. Collateral information on the included compounds was gathered through manual searches in PubMed and press releases. Results Sixteen compounds were identified; four compounds (ulotaront, xanomeline/trospium chloride, vabicaserin, and roluperidone) were investigated as monotherapy and the remaining 12 (pimavanserin, bitopertin, BI 425809, encenicline, tropisetron, pregnenolone, D-serine, estradiol, tolcapone, valacyclovir, cannabidiol, and rimonabant) were examined as add-on therapy. Compared to the placebo, ulotaront, xanomeline/trospium chloride, vabicaserin, bitopertin, estradiol, cannabidiol, rimonabant, and D-serine showed efficacy for positive symptoms; roluperidone and pimavanserin were effective for negative symptoms; and encenicline, tropisetron, pregnenolone, tolcapone, BI 425809, and valacyclovir improved cognitive function. Discussion Compounds that function differently from existing antipsychotics may offer novel symptom-specific therapeutic strategies for patients with schizophrenia.

01 Jun 2023·European journal of pharmacology

The enhancing effect of 5-HT on phasic contractions of human isolated distal ureter and the mechanisms mediating these effects

Article

Author: Liu, Lei ; Zhao, Mengmeng ; Ding, Ning ; Zhang, Xiulin ; Song, Wei ; Liu, Jiaxin ; Yan, Jieke ; Zu, Shulu ; Liu, Jianing ; Xu, Yang ; Wen, Jiliang ; Liu, Hanwen

5-Hydroxytryptamine (5-HT) can enhance human ureteral contractions. However, the mediating receptors have not been clarified. This study sought to further characterize the mediating receptors using several selective antagonists and agonists. Human distal ureters were obtained from 96 patients undergoing cystectomy. The mRNA expression levels of 5-HT receptors were examined using RT-qPCR experiments. The phasic contractions of ureter strips, either spontaneous or evoked with neurokinin, were recorded in an organ bath. Among the 13 5-HT receptors, 5-HT_2A and 5-HT_2C receptors showed the highest mRNA expression levels. 5-HT (10^-7-10^-4 M) increased the frequency and baseline tension of phasic contractions in a concentration-dependent manner. However, a desensitization effect was observed. The 5-HT_2C receptor selective antagonist, SB242084 (10,30,100 nM), shifted the 5-HT concentration-response curves (frequency and baseline tension) rightward with a pA2 value of 8.05 and 7.75, respectively. 5-HT_2C receptor selective agonist, vabicaserin, increased contraction frequency with an Emax of 35% of 5-HT. 5-HT_2A receptor selective antagonist, volinanserin (1,10,100 nM), only reduced baseline tension with a pA2 of 8.18. The selective antagonists of 5-HT_1A, 1B, 1D, 2B, 3, 4, 5, 6, and 7 had no antagonism. Blockade of voltage-gated sodium channels, α1-adrenergic receptors, adrenergic neurotransmission, and neurokinin-2 receptors using tetrodotoxin, tamsulosin, guanethidine, and Men10376, respectively, and desensitization of sensory afferents using capsaicin (100 μM), significantly reduced 5-HT effects. We conclude that 5-HT enhanced ureteral phasic contractions mainly by activating 5-HT_2C and 5-HT_2A receptors. Sympathetic nerve and sensory afferents partly contributed to 5-HT effects. 5-HT_2C and 5-HT_2A receptors could be promising targets for ureteral stone expulsion.

01 Jun 2021·Current topics in medicinal chemistryQ4 · MEDICINE

New Pharmacological Targets for the Treatment of Schizophrenia: A Literature Review

Q4 · MEDICINE

Review

Author: Ricci, Fabiana ; Magnifico, Giuseppe ; Rinaldi, Angelo ; De Berardis, Domenico ; Ventriglio, Antonio ; Delle Monache, Sonia ; Gianfelice, Giulia ; Piccininni, Carla ; Borraccino, Luisa ; Bellomo, Antonello ; Cuoco, Federica ; Fornaro, Michele

Background::

The pharmacological treatment of schizophrenia is currently based on the employment of antipsychotic medications showing an antagonism of dopaminergic and serotoninergic inhibitors. 20-40% of patients are drug-resistant or residually symptomatic in the long-term antipsychotic treatment, and new strategies are needed for improving their functional and cognitive impairment.

Methods::

This systematic review has summarized evidences from the literature regarding the newer pharmacological targets proposed for the treatment of psychosis. We included 128 peer-reviewed articles and 5 other relevant sources published from 2002 to 2020 on PubMed EMBASE, The Cochrane Library, and Google Scholar.

Results::

The possible role of glutamate and its receptors as targets of the antipsychotic mechanism of action has been described. Glutamatergic neurotransmission and NMDA receptors hypofunction are involved in the neurobiological explanatory model of psychosis and possibly targeted for the successful treatment of cognitive and residual symptoms. Results show an efficacy of D-cycloserine (antagonist at the Glycine site of the NMDA-R) in the treatment of negative symptoms of schizophrenia as well as Memantine (NMDA- Receptor antagonist) for cognition and psychopathology. The putative antipsychotic effect of cannabidiol on positive symptoms and cognition will also be discussed. The action on serotoninergic and GABAergic receptors will be considered as a new pharmacological target, with a possible efficacy of Vabicaserin on symptoms of psychosis. Mynocicline has shown to induce improvements in cognitive symptoms in schizophrenia, as well as Erythropoietin. Oxytocin has been reported to have an antipsychotic-like effect; moreover, COX-2 inhibitors lead to a reduction in positive symptoms of psychosis, specifically in the first episode of illness.

Conclusion::

This narrative report suggests a promising role of new agents in the treatment of Schizophrenia; however, more research is needed to approve their clinical employment.

100 Deals associated with Vabicaserin Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D06660	Vabicaserin Hydrochloride	-	DB12071

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Schizophrenia	Phase 2	US	Pfizer Inc.	01 Dec 2007
Schizophrenia	Phase 2	CA	Pfizer Inc.	01 Dec 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00563706 (CTgov)	Phase 2	Schizophrenia	199	vabicaserin (SCA-136)+placebo (Placebo)	duuabrbqxn(tjaselsfjx) = cwamuujpvs jphfffznhz (ockxtodpjt, jyraevsrhh - ysgclovhko) View more	-	20 Mar 2014
				Vabicaserin (Vabicaserin 50 mg)	duuabrbqxn(tjaselsfjx) = xsjspltybv jphfffznhz (ockxtodpjt, qomiavaakg - fwhirbzalk) View more