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Details

Stereochemistry ABSOLUTE
Molecular Formula C11H21N.ClH
Molecular Weight 203.7524
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEXMECAMYLAMINE HYDROCHLORIDE

SMILES

CC1(C)[C@@]2([H])CC[C@]([H])(C2)[C@]1(C)NC.Cl

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 167.2916
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 3 / 3
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula ClH
Molecular Weight 36.4609
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
33.16 ng/mL
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
537.68 ng × h/mL
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
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
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.4 h
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
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
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
PubMed

PubMed

TitleDatePubMed
Differential pharmacologies of mecamylamine enantiomers: positive allosteric modulation and noncompetitive inhibition.
2009 Feb
Clinical Efficacy and Tolerability of the Nicotinic Channel Modulator Dexmecamylamine in Subjects with Overactive Bladder.
2015 Nov
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
Patents

Patents

Sample Use Guides

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
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 Jun 26 05:46:15 UTC 2021
Edited
by admin
on Sat Jun 26 05:46:15 UTC 2021
Record UNII
W3079LM7E7
Record Status Validated (UNII)
Record Version
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Name Type Language
DEXMECAMYLAMINE HYDROCHLORIDE
USAN   WHO-DD  
USAN  
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
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
FDA UNII
W3079LM7E7
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
ChEMBL
CHEMBL2103881
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
MERCK INDEX
M7113
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY Merck Index
CAS
107596-30-5
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
DRUG BANK
DBSALT002079
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
NCI_THESAURUS
C169898
Created by admin on Sat Jun 26 05:46:15 UTC 2021 , Edited by admin on Sat Jun 26 05:46:15 UTC 2021
PRIMARY
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