Delving into the Latest Updates on Salvinorin A with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Target

κ opioid receptor

Mechanism

κ opioid receptor agonists(Kappa opioid receptor agonists)

Therapeutic Areas

Other Diseases

Active Indication

Depressive Disorder

Inactive Indication

Depressive Disorder, Treatment-ResistantVasospasm, Intracranial

Originator Organization

University of Pennsylvania

Active Organization

Intelgenx Corp.

Inactive Organization

University of PennsylvaniaRevixia Life Sciences, Inc.Neurokappa Therapeutics

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

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Structure

Molecular FormulaC23H28O8

InChIKeyOBSYBRPAKCASQB-AGQYDFLVSA-N

CAS Registry83729-01-5

This study will investigate the effects of salvinorin A on human brain activity and connectivity using functional magnetic resonance imaging (fMRI) methods. An inhalation route of administration will be used as it is the most common route for contemporary use of Salvia divinorum, a plant containing salvinorin A.

Start Date14 Dec 2017

Sponsor / Collaborator

The Johns Hopkins University

[+1]

NCT01149824 / CompletedNot ApplicableIIT

A Double Blind Placebo Controlled Ascending Dose Pharmacodynamic and Tolerability Study of 100 to 4000 µg of Sublingual Salvinorin A

In this study, our aim is to determine an active but tolerable sublingual dose (range 100 to 4000 µg) of Salvinorin A (SA) in experienced subjects. This study is an ascending-dose, placebo-controlled, single-site design in 8 Salvia-experienced subjects. Subjects will receive SA doses from 0-4000 µg. Doses will be separated by at least one day. The first two doses (0 and 100µg) will be double-blinded while the last four (250, 500, 1000, 2000 and 4000µg) will be single-blind.

Start Date01 Jun 2009

Sponsor / Collaborator

California Pacific Medical Center Research Institute

NCT00700596 / CompletedEarly Phase 1IIT

Psychotomimetic Effects of Kappa Opioid Receptor Agonist Salvinorin A in Healthy Controls

This study evaluates the effects of Salvinorin A (SA). SA is the active ingredient of the plant Salvia divinorum that is known to have been used by Mexican Indians as part of religious rituals. The purpose of this project is to understand what people experience when they consume Salvinorin A.

Start Date12 Feb 2009

Sponsor / Collaborator

Yale University

[+1]

100 Clinical Results associated with Salvinorin A

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100 Translational Medicine associated with Salvinorin A

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100 Patents (Medical) associated with Salvinorin A

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328

Literatures (Medical) associated with Salvinorin A

01 Dec 2024·Journal of Ethnopharmacology

Salvinorin A ameliorates pilocarpine-induced seizures by regulating hippocampal microglia polarization

Article

Author: Yang, Jiao ; Wu, Tong-Xuan ; Zhou, Chao ; Ji, Miao-Jin ; Cai, Ji-Heng ; Gao, Zhi-Qiang ; Wu, Qi

ETHNOPHARMACOLOGICAL RELEVANCESalvia divinorum (Epling and Játiva) is a psychoactive plant traditionally used by the Latinos for various medicinal purposes. Salvinorin A (Sal A), the main bioactive constituent of S. divinorum, is a natural highly selective kappa opioid receptor (KOR) agonist. Considering the anti-inflammatory effect of S. divinorum and endogenous hippocampal dynorphin/ kappa opioid receptor (KOR) system playing an anticonvulsant function, we hypothesis that Sal A can be a potential candidate to treat epilepsy. Here, we identified whether Sal A ameliorated epileptic seizures and neuronal damages in animal model and in vitro model and investigated its underlying mechanisms.MATERIALS AND METHODSMice epilepsy model was induced by pilocarpine following seizures assessed by Racine classification. Hippocampus tissues were obtained for genetic, protein, and histological investigation. Furthermore, lipopolysaccharide (LPS)-activated BV2 microglial cells were utilized to validate the anti-inflammatory and microglia polarization regulation effects of Sal A.RESULTSSal A treatment significantly prolonged the latency to status epileptics (SE) and shortened the duration of SE in the pilocarpine-induced model. It also alleviated neuronal damages via activation of the AMPK/JNK/p-38 MAPK pathway and inhibition of apoptosis-related protein in hippocampus tissues. Furthermore, Sal A dose-dependently reduced microglia-mediated expression of pro-inflammatory cytokines and increased anti-inflammatory factors levels in SE mice and LPS-activated BV2 microglial cells by regulating microglia polarization. In addition, the effect of Sal A in vitro was totally blocked by KOR antagonist nor-BNI.CONCLUSIONSal A treatment protects against epileptic seizures and neuronal damages in pilocarpine-induced models by suppressing the inflammation response through regulating microglial M1/M2 polarization. This study might serve as a theoretical basis for clinical applications of Sal A and its analogs and provide a new insight into the development of anti-seizure drugs.

01 Nov 2024·Nature Chemistry

The original caretakers of salvinorin A and recognizing Indigenous contributions to science

Article

Author: Clay, Khalyd J. ; Shenvi, Ryan A ; Clay, Khalyd J ; Shenvi, Ryan A.

Much natural-product-based drug discovery has depended on the practices of Indigenous Peoples, who have sometimes invested centuries of care into the cultivation and use of plant or fungal matter.However, the contributions of the original discoverers can be lost as the natural products are developed into pharmaceutical products.

01 Sep 2024·Physiologia Plantarum

Identification of clerodane diterpene modifying cytochrome P450 (CYP728D26) in Salvia divinorum ‐ en route to psychotropic salvinorin A biosynthesis

Article

Author: Kumar, Rahul ; Ro, Dae‐Kyun ; Li, Liang ; Ngo, Iris ; Kwon, Moonhyuk ; Kim, Seon‐Won

AbstractSalvia divinorum is a hallucinogenic plant native to the Oaxaca in Mexico. The active ingredient for psychotropic effects in this plant is salvinorin A, a potent and highly selective κ‐opioid receptor agonist. Salvinorin A is distinct from other well‐known opioids, such as morphine and codeine, in that it is a non‐nitrogenous diterpenoid with no affinity for μ‐opioid receptor, the prime receptor of alkaloidal opioids. A terpene opioid that selectively targets a new opioid receptor (κ‐opioid receptor) can be instrumental in developing alternative analgesics. Elucidation of the salvinorin A biosynthetic pathway can help bio‐manufacture diverse semi‐synthetic derivatives of salvinorin A but, to date, only two enzymes in the Salvinorin A pathway have been identified. Here, we identify CYP728D26 that catalyzes a C18 oxygenation on crotonolide G, which bears a clerodane backbone. Biochemical identity of CYP728D26 was validated by in vivo reconstitution in yeast, 1H‐ and 13C‐NMR analyses of the purified product, and kinetic analysis of CYP728D26 with a Km value of 13.9 μM. Beyond the single oxygenation on C18, collision‐induced dissociation analysis suggested two additional oxygenations are catalyzed by CYP728D26 to form crotonoldie G acid, although this carboxylic acid form is a minor product. Its close homologue CYP728D25 exhibited a C1‐hydroxylation on the clerodane backbone in a reconstituted yeast system. However, CYP728D25 showed no activity in in vitro assays. This result implies that catalytic activities observed from overexpression systems should be interpreted cautiously. This work identified a new CYP catalyst and advanced our knowledge of salvinorin A biosynthesis.

100 Deals associated with Salvinorin A

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External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Treatment-Resistant	IND Application	US	Revixia Life Sciences, Inc.	28 Mar 2022
Vasospasm, Intracranial	IND Application	-	Neurokappa Therapeutics	-
Vasospasm, Intracranial	IND Application	-	University of Pennsylvania	-
Depressive Disorder	Preclinical	CA	Intelgenx Corp.	19 May 2022

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03418714 (CTgov)	Phase 1/2	Drug-Related Side Effects and Adverse Reactions	13	Salvinorin A	datbwkekjp(eyngrlcyru) = wykouksvtf oddsunzafu (nxkmbekfar, dqujbkqbfk - wteovvyual) View more	-	04 Mar 2021