| 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
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
| Molecular Formula | C11H21N |
| Molecular Weight | 167.2911 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| 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 |
MOL RATIO
1 MOL RATIO (average) |
| 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.
CNS Activity
Originator
Approval Year
Sourcing
PubMed
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.
