Delving into the Latest Updates on Dexmecamylamine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Dexmecamylamine, Dexmecamylamine hydrochloride (USAN), S(+)-mecamylamine

+ [4]

Target

nAChR α4/β2/α5 x nAChRα3&β4

Action

antagonists

Mechanism

Nicotinic acetylcholine receptor alpha4/beta2/alpha5 antagonists, α3β4 receptor antagonists(Neuronal acetylcholine receptor; alpha3/beta4 antagonists)

Therapeutic Areas

Other DiseasesSkin and Musculoskeletal DiseasesUrogenital Diseases+ [1]

Active Indication-

Inactive Indication

Depressive Disorder, MajorDrug abuseHyperhidrosis+ [3]

Originator Organization

Catalyst Biosciences, Inc.

Active Organization-

Inactive Organization

AstraZeneca PLCTargacept, Inc.

Atacama Therapeutics, Inc.Startup

Drug Highest PhaseDiscontinuedPhase 3

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC11H22ClN

InChIKeyPKVZBNCYEICAQP-GSTSRXQZSA-N

CAS Registry107596-30-5

View All Structures (2)

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group comparison study of AT-5214 in subjects with moderate to severe primary palmar hyperhidrosis (sweaty palms). This study will compare two different oral (tablet) doses of AT-5214 (study drug) versus a matched placebo. Approximately 120 subjects will be enrolled at approximately 10 study sites.

Start Date31 Jan 2020

Sponsor / Collaborator

Atacama Therapeutics, Inc.Startup

NCT03404570

/ CompletedPhase 2

A Double-Blind, Randomized, Placebo-Controlled Exploratory Study to Assess the Efficacy and Safety of TC-5214 in the Treatment of Subjects With Moderate to Severe Palmar Hyperhidrosis

This is a pilot exploratory study to evaluate the safety and efficacy of TC-5214 in subjects with palmar hyperhidrosis.

Start Date21 Dec 2017

Sponsor / Collaborator

Atacama Therapeutics, Inc.Startup

100 Clinical Results associated with Dexmecamylamine Hydrochloride

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100 Translational Medicine associated with Dexmecamylamine Hydrochloride

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100 Patents (Medical) associated with Dexmecamylamine Hydrochloride

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32

Literatures (Medical) associated with Dexmecamylamine Hydrochloride

01 Dec 2024·Neuroscience

S-(+)-mecamylamine increases the firing rate of serotonin neurons and diminishes depressive-like behaviors in an animal model of stress

Article

Author: Hernández-González, O. ; Rojano-Posada, Y. ; Garduño, J. ; Francia-Ramírez, D ; Rojano-Posada, Y ; Ortega-Tinoco, S ; Francia-Ramírez, D. ; Mondragón-García, A. ; Mondragón-García, A ; Ramírez-Sánchez, E. ; Verdugo-Díaz, L ; Ortega-Tinoco, S. ; Ramírez-Sánchez, E ; Hernández-López, S ; Garduño, J ; Hernández-López, S. ; Verdugo-Díaz, L. ; Hernández-González, O

Mecamylamine, a noncompetitive blocker of nicotinic acetylcholine receptors (nAChRs), is the racemic mixture of two stereoisomers: S-(+)-mecamylamine (S-mec) and R-(-)-mecamylamine (R-mec), with distinct interactions with α4β2 nAChRs. It has been shown that mecamylamine increases glutamate release and excites serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN). In this study, we separately evaluated the effects of S-mec and R-mec on 5-HT neuron excitability. S-mec (3 μM) increased firing frequency by 40 %, while R-mec (3 μM) raised it by only 22 %. S-mec acts as a positive allosteric modulator on high-sensitivity (HS) α4β2 nAChRs at glutamate terminals, enhancing spontaneous excitatory postsynaptic currents (sEPSCs) in 5-HT neurons. Conversely, R-mec decreased sEPSCs by blocking HS α4β2 nAChRs and reduced GABA-mediated inhibitory currents (sIPSCs) by blocking α7 nAChRs at GABAergic terminals. These mechanisms make S-mec more effective than R-mec in enhancing 5-HT neuron firing. Moreover, combining S-mec with TC-2559, a selective agonist of HS α4β2 nAChRs, increased firing frequency by 65 %, exceeding the effect of S-mec alone. To validate these findings, we evaluated the antidepressant effects of S-mec (1 mg/kg) combined with TC-2559 or RJR-2403, another α4β2 nAChR agonist. This combination successfully reduced depression-like behaviors, suggesting a potential treatment strategy for patients resistant to conventional antidepressants.

01 Jul 2022·PsychopharmacologyQ3 · MEDICINE

Ropanicant (SUVN-911), an α4β2 nicotinic acetylcholine receptor antagonist intended for the treatment of depressive disorders: pharmacological, behavioral, and neurochemical characterization

Q3 · MEDICINE

Article

Author: Abraham, Renny ; Thentu, Jagadeesh Babu ; Palacharla, Veera Raghava Chowdary ; Jayarajan, Pradeep ; Mohammed, Abdul Rasheed ; Pandey, Santosh Kumar ; Goura, Venkatesh ; Subramanian, Ramkumar ; Kallepalli, Rajesh ; Jasti, Venkat ; Petlu, Surendra ; Gagginapally, Shankar Reddy ; Medapati, Rajesh Babu ; Tadiparthi, Jayaprakash ; Goyal, Vinod Kumar ; Nirogi, Ramakrishna

RATIONALERopanicant (SUVN-911) (3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo (3.1.0) hexane hydrochloride) is a novel α4β2 nicotinic acetylcholine receptor (nAChR) antagonist being developed for the treatment of depressive disorders.OBJECTIVESPharmacological and neurochemical characterization of Ropanicant to support a potential molecule for the treatment of depressive disorders.METHODSRopanicant was assessed for antidepressant-like activity using the rat forced swimming test (FST) and differential reinforcement of low rate -72 s (DRL-72 s). Alleviation of anhedonia was assessed in chronic mild stress model using sucrose preference test. To understand the mechanism of action, serotonin levels, ionized calcium-binding adaptor molecule 1 (Iba1), and brain-derived neurotrophic factor (BDNF) were determined. The onset of antidepressant-like activity was determined using the reduction in submissive behavior assay. The effects on cognition and sexual functions were assessed using the object recognition task and sexual dysfunction assay respectively. Interaction of Ropanicant, TC-5214, and methyllycaconitine (MLA) with citalopram was investigated individually in mice FST.RESULTSRopanicant exhibited antidepressant like properties in the FST and DRL-72 s. A significant reduction in anhedonia was observed in the sucrose preference test. Oral administration of Ropanicant produced a significant increase in serotonin and BDNF levels, with a reduction in the Iba1 activity. The onset of antidepressant like effect with Ropanicant was within a week of treatment, and was devoid of cognitive dulling and sexual dysfunction. While Ropanicant potentiated the effect of citalopram in FST, such an effect was not observed with MLA or TC-5214.CONCLUSIONSPreclinical studies with Ropanicant support the likelihood of its therapeutic utility in the treatment of depressive disorders.

01 Mar 2022·Molecular PsychiatryQ1 · MEDICINE

Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs

Q1 · MEDICINE

Article

Author: Pineda, Cristiana M ; Vanopdenbosch, Laura ; Islam, Ashraful ; Crouse, Richard B ; Thompson, David C ; Mose, Tenna N ; Zhou, Wenliang ; Bentham, Matthew P ; Mineur, Yann S ; Ogbejesi, Chika ; Etherington, Ian M ; Picciotto, Marina R

Acetylcholine (ACh) levels are elevated in actively depressed subjects. Conversely, antagonism of either nicotinic or muscarinic ACh receptors can have antidepressant effects in humans and decrease stress-relevant behaviors in rodents. Consistent with a role for ACh in mediating maladaptive responses to stress, brain ACh levels increase in response to stressful challenges, whereas systemically blocking acetylcholinesterase (AChE, the primary ACh degradative enzyme) elicits depression-like symptoms in human subjects, and selectively blocking AChE in the hippocampus increases relevant behaviors in rodents. We used an ACh sensor to characterize stress-evoked ACh release, then used chemogenetic, optogenetic and pharmacological approaches to determine whether cholinergic inputs from the medial septum/diagonal bands of Broca (MSDBB) or ChAT-positive neurons intrinsic to the hippocampus mediate stress-relevant behaviors in mice. Chemogenetic inhibition or activation of MSDBB cholinergic neurons did not result in significant behavioral effects, while inhibition attenuated the behavioral effects of physostigmine. In contrast, optogenetic stimulation of septohippocampal terminals or selective chemogenetic activation of ChAT-positive inputs to hippocampus increased stress-related behaviors. Finally, stimulation of sparse ChAT-positive hippocampal neurons increased stress-related behaviors in one ChAT-Cre line, which were attenuated by local infusion of cholinergic antagonists. These studies suggest that ACh signaling results in maladaptive behavioral responses to stress if the balance of signaling is shifted toward increased hippocampal engagement.

100 Deals associated with Dexmecamylamine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D10112	-	-	DB11807

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Depressive Disorder, Major	Phase 3	United States	Targacept, Inc.	01 Jun 2010
Depressive Disorder, Major	Phase 3	India	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	India	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	United States	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	United States	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	Puerto Rico	Targacept, Inc.	01 Jun 2010
Depressive Disorder, Major	Phase 3	Puerto Rico	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	Puerto Rico	Targacept, Inc.	01 Jun 2010
Depressive Disorder, Major	Phase 3	Puerto Rico	AstraZeneca PLC	01 Jun 2010
Depressive Disorder, Major	Phase 3	United States	Targacept, Inc.	01 Jun 2010

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01153347 (CTgov)	Phase 3	Depressive Disorder, Major	2,409	TC-5214 (0.5 mg BID TC-5214)	hncfrdgqak(dvhnwjyrsm) = graemwwmpu duyzpmwayb (vpqswwqamn, mdscghbiyc - mmnawbdnxq) View more	-	20 Nov 2012
				TC-5214 (2 mg BID TC-5214)	hncfrdgqak(dvhnwjyrsm) = eougwipzsa duyzpmwayb (vpqswwqamn, sbxlhtwzqw - uqhoosswun) View more
NCT01180400 (CTgov)	Phase 3	Depressive Disorder, Major	295	TC-5214 (TC-5214)	dgrhzoyrok(ergjsmdquf) = pojgdyfkow kbgfgulrwb (lsbnmhzpur, ysezxtmyvy - jbmzsogrji) View more	-	20 Nov 2012
				Placebo (Placebo)	dgrhzoyrok(ergjsmdquf) = wpwbvwmrcc kbgfgulrwb (lsbnmhzpur, aoovjijdjy - zsuenpictu) View more
NCT01157078 (CTgov)	Phase 3	Major depressive disorder, moderate (MDD) \| Depressive Disorder, Major	319	TC-5214 (TC-5214)	jgyuggminy(piaicwlgqu) = nnkvanwsma ffgkvcqzol (cyrmedadeo, tjmxydlcxh - myjreigdok) View more	-	20 Nov 2012
				Placebo (Placebo)	jgyuggminy(piaicwlgqu) = cajzynwqsd ffgkvcqzol (cyrmedadeo, ynprwkszjv - pivymmzihi) View more
NCT01197508 (CTgov)	Phase 3	Depressive Disorder, Major	696	TC-5214 (0.1 mg BID TC-5214)	vhrywkxecn(olygavkoss) = aahrnulsps ooxvqphgna (wisrkvhzyq, ithzdybmuo - mydljdgxeh) View more	-	29 Oct 2012
				TC-5214 (1 mg BID TC-5214)	vhrywkxecn(olygavkoss) = oejvahpuwa ooxvqphgna (wisrkvhzyq, jasqfaxjar - ktyyppkhgo) View more
NCT01152554 (CTgov)	Phase 3	Depressive Disorder, Major	813	Serotonin+TC-5214 (TC-5214)	ijkanalsuz(dkigtuifbs) = ruqwbfuiqg vxzveicopn (hkbgtuhaif, exrrjftlwj - yltvumsqex) View more	-	29 Oct 2012
				Selective serotonin reuptake (Placebo)	ijkanalsuz(dkigtuifbs) = xfghnhnxew vxzveicopn (hkbgtuhaif, zqzzixcgtd - kmzvwhbywl) View more