DEXMECAMYLAMINE HYDROCHLORIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C11H21N.ClH
Molecular Weight	203.752
Optical Activity	( + )
Defined Stereocenters	3 / 3
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DEXMECAMYLAMINE HYDROCHLORIDE

Structure Search

SMILES

Cl.CN[C@@]1(C)[C@@H]2CC[C@@H](C2)C1(C)C

InChI

InChIKey=PKVZBNCYEICAQP-GSTSRXQZSA-N

InChI=1S/C11H21N.ClH/c1-10(2)8-5-6-9(7-8)11(10,3)12-4;/h8-9,12H,5-7H2,1-4H3;1H/t8-,9+,11-;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C11H21N
Molecular Weight	167.2911
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	3 / 3
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.businesswire.com/news/home/20140728006104/en/Targacept-Discontinue-TC-5214-Overactive-Bladder-Program | https://www.ncbi.nlm.nih.gov/pubmed/25602163 | https://www.ncbi.nlm.nih.gov/pubmed/18957576

Dexmecamylamine (TC-5214, also known, as S isomer of mecamylamine) is a positive allosteric modulator of α4β2 neuronal nicotinic receptors, rather than an open-channel blocker. It was evaluated as a potential adjunct treatment for patients with major depressive disorder (MDD). TC-5214 was generally well tolerated, however, the studies were not supportive of an antidepressant effect for TC-5214 in patients with MDD and inadequate response to prior antidepressant therapy. The Phase 2b clinical trial of TC-5214 for the treatment for overactive bladder (OAB) revealed the high dose of TC-5214 demonstrated mixed results on the co-primary endpoints by providing a statistically significant reduction in micturition frequency and an improvement that did not reach statistical significance on episodes of urinary incontinence. As a consequence of these results, this drug was discontinuing further development of TC-5214 in OAB. The study for using TC-5214 in patients with refractory hypertension was also terminated.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Neuronal acetylcholine receptor; alpha4/beta2 76 Target ID: CHEMBL1907589 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18957576	Positive Allosteric Modulator 179

Conditions

Condition	Modality	Highest Phase	Product
Major depressive disorder 173 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25602163	Primary	Phase II 1132	Unknown Approved Use Unknown
Overactive bladder 38 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26073872	Primary	Phase II 1132	Unknown Approved Use Unknown
Refractory hypertension 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00899977	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
33.16 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
31.544 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.606 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
537.68 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
767.28 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
248.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
10.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
14 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	8 mg single, oral dose: 8 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24760402	2 mg single, oral dose: 2 mg route of administration: Oral experiment type: SINGLE co-administered:	DEXMECAMYLAMINE plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34256	https://www.001chemical.com/chem/search?q=DY34256
001 Chemical	DY34257	https://www.001chemical.com/chem/search?q=DY34257
Alinda	ALBB-023410	http://alinda.ru/finechem_en_.html?i=ALBB-023410
BOC Sciences	107538-05-6	http://www.bocsci.com/description.asp?cas=107538-05-6
BioSynth	Q-201341	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/Q-201341
Chemspace	CSC015645827	https://chem-space.com/CSC015645827
Chemspace	CSC015659858	https://chem-space.com/CSC015659858
Compound Cloud	12358971
Compound Cloud	12358972
Enamine	BBV-77631107	http://www.enaminestore.com/catalog/BBV-77631107
Enamine	BBV-77652981	http://www.enaminestore.com/catalog/BBV-77652981
Hangzhou Yuhao Chemical Technology	RT3984
Lan Pharmatech	LQT-B47398
Molcore	MC34256	http://www.molcore.com/CatMC34256.html
Molcore	MC34257	http://www.molcore.com/CatMC34257.html
Toronto Research Chemicals	M202595	https://www.trc-canada.com/product-detail/?CatNum=M202595
eMolecules	43050930	https://orderbb.emolecules.com/search/#?query=43050930
eMolecules	46011392	https://orderbb.emolecules.com/search/#?query=46011392

PubMed

Title	Date	PubMed
Differential pharmacologies of mecamylamine enantiomers: positive allosteric modulation and noncompetitive inhibition.	2009 Feb	18957576
Clinical Efficacy and Tolerability of the Nicotinic Channel Modulator Dexmecamylamine in Subjects with Overactive Bladder.	2015 Nov	26073872
Two Phase III randomised double-blind studies of fixed-dose TC-5214 (dexmecamylamine) adjunct to ongoing antidepressant therapy in patients with major depressive disorder and an inadequate response to prior antidepressant therapy.	2015 Oct	25602163

Patents

Sample Use Guides

In Vivo Use Guide

8-week randomised, active treatment with twice-daily TC-5214 (dexmecamylamine) (0.5, 2 or 4 mg in Study 004; 0.1, 1 or 4 mg in Study 005) or placebo

Route of Administration: Oral

In Vitro Use Guide

To determine whether the high-sensitivity (HS) and low-sensitivity (LS) isoforms of the human α4β2 neuronal nicotinic receptors (NNRs) components display differences in their pharmacological profiles with respect to mecamylamine sensitivity, it was conducted nicotine concentration-response studies in the absence or presence of either of the enantiomers, TC-5214 (dexmecamylamine) or TC-5213. The analysis indicated that the relationship between inhibition of peak current produced by 1 μM TC-5214, and nicotine concentration was not linear. Responses induced by concentrations of nicotine up to 1 μM (primarily reflecting HS activation) were not appreciably inhibited by TC-5214. In comparison, responses to concentrations of nicotine greater than 1 μM (primarily reflecting LS activation) were profoundly inhibited. Increasing the concentration of TC-5214 to 2 μM resulted in a more complete and nonselective inhibition of responses at all nicotine concentrations applied. These results suggest that at low concentrations, TC-5214 preferentially inhibits LS α4β2 receptors. TC-5213 also inhibited responses to relatively high concentrations of nicotine (10 μM), but this effect was not found to be statistically significant.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 01:47:32 UTC 2023` Edited by `admin` on `Sat Dec 16 01:47:32 UTC 2023`
Record UNII	W3079LM7E7
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DEXMECAMYLAMINE HYDROCHLORIDE

Official Name

English

BICYCLO(2.2.1)HEPTAN-2-AMINE, N,2,3,3-TETRAMETHYL-, HYDROCHLORIDE, (1R-EXO)-

Systematic Name

English

NIH-11008

Code

English

(1R,2S,4S)-N,2,3,3-Tetramethylbicyclo[2.2.1]heptan-2-amine hydrochloride

Systematic Name

English

DEXMECAMYLAMINE HYDROCHLORIDE [USAN]

Common Name

English

Dexmecamylamine hydrochloride [WHO-DD]

Common Name

English

MECAMYLAMINE S-(+)-FORM HYDROCHLORIDE [MI]

Common Name

English

Code System Code Type Description

PUBCHEM

12358971