U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C11H21N
Molecular Weight 167.2916
Optical Activity ( + / - )
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MECAMYLAMINE

SMILES

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

InChI

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

HIDE SMILES / InChI
Mecamylamine (Inversine), the first orally available antihypertensive agent, is now rarely used. Introduced as a therapeutic agent for the treatment of hypertension in the 1950s, mecamylamine was the first useful ganglionic blocking agent that was not a quarternary ammonium compound. Mecamylamine is indicated for the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Mecamylamine reduces blood pressure in both normotensive and hypertensive individuals. A small oral dosage often produces a smooth and predictable reduction of blood pressure. Although this antihypertensive effect is predominantly orthostatic, the supine blood pressure is also significantly reduced. Mecamylamine is a nicotinic parasympathetic ganglionic blocker. Mecamylamine administration produces several deleterious side-effects at therapeutically relevant doses. As such, mecamylamine’s use as an antihypertensive agent was phased out, except in severe hypertension. Mecamylamine easily traverses the blood-brain barrier to reach the central nervous system (CNS), where it acts as a nicotinic acetylcholine receptor (nAChR) antagonist, inhibiting all known nAChR subtypes. Since nAChRs play a major role in numerous physiological and pathological processes, it is not surprising that mecamylamine has been evaluated for its potential therapeutic effects in a wide variety of CNS disorders, including addiction.

CNS Activity

Curator's Comment:: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier.

Originator

Curator's Comment:: Mecamylamine was introduced originally by Merck & Co., Inc. as an antihypertensive agent # Merck & Co.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
INVERSINE

Approved Use

For the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension.

Launch Date

-4.36665614E11
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
7.89 ng/mL
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
23.68 ng/mL
7.5 mg single, oral
dose: 7.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
115.3 ng × h/mL
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
352.3 ng × h/mL
7.5 mg single, oral
dose: 7.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
149.3 ng × h/mL
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
467.3 ng × h/mL
7.5 mg single, oral
dose: 7.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
150.6 ng × h/mL
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
472.6 ng × h/mL
7.5 mg single, oral
dose: 7.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
10.1 h
2.5 mg single, oral
dose: 2.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
10.5 h
7.5 mg single, oral
dose: 7.5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MECAMYLAMINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Other AEs: Nausea, Somnolence...
Other AEs:
Nausea (10.3%)
Somnolence (34.5%)
Dizziness (17.2%)
Fatigue (24.1%)
Orthostatic hypotension (27.6%)
Headache (10.3%)
Application site pruritus (3.4%)
Vision blurred (17.2%)
Constipation (13.8%)
Vomiting (3.4%)
Dizziness postural (3.4%)
Abdominal pain (10.3%)
Abdominal distension (3.4%)
Sources:
5 mg 2 times / day multiple, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: multiple
Dose: 5 mg, 2 times / day
Sources:
healthy, mean age 34.1 years
n = 24
Health Status: healthy
Age Group: mean age 34.1 years
Sex: M+F
Population Size: 24
Sources:
DLT: Abdominal pain, Constipation...
Dose limiting toxicities:
Abdominal pain (4.2%)
Constipation (4.2%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Abdominal pain 10.3%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Headache 10.3%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Nausea 10.3%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Constipation 13.8%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Dizziness 17.2%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Vision blurred 17.2%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Fatigue 24.1%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Orthostatic hypotension 27.6%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Abdominal distension 3.4%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Application site pruritus 3.4%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Dizziness postural 3.4%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Vomiting 3.4%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Somnolence 34.5%
30 mg 1 times / day single, oral
Highest studied dose
Dose: 30 mg, 1 times / day
Route: oral
Route: single
Dose: 30 mg, 1 times / day
Sources:
healthy, 18 -45 years
n = 29
Health Status: healthy
Age Group: 18 -45 years
Sex: M
Population Size: 29
Sources:
Abdominal pain 4.2%
DLT
5 mg 2 times / day multiple, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: multiple
Dose: 5 mg, 2 times / day
Sources:
healthy, mean age 34.1 years
n = 24
Health Status: healthy
Age Group: mean age 34.1 years
Sex: M+F
Population Size: 24
Sources:
Constipation 4.2%
DLT
5 mg 2 times / day multiple, oral
Recommended
Dose: 5 mg, 2 times / day
Route: oral
Route: multiple
Dose: 5 mg, 2 times / day
Sources:
healthy, mean age 34.1 years
n = 24
Health Status: healthy
Age Group: mean age 34.1 years
Sex: M+F
Population Size: 24
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Effects of ganglion blocking agents on nicotine extensor convulsions and lethality in mice.
1969 Sep
Effect of cholingeric drugs on methadone-induced catalepsy and stereotypies in rats treated chronically with methadone.
1976 Oct
Pharmacokinetics of nicotine in adult and infant mice.
1977 Dec
Neuropharmacology of the parasitic trematode, Schistosoma mansoni.
1983 Jan
Mecamylamine blockade of nicotine responses: evidence for two brain nicotinic receptors.
1986 Jun
The effect of cholinergic stimulation in the nucleus accumbens on locomotor behavior.
1988 Feb 16
Nicotine-induced tail-tremor and drug effects.
1989 Dec
Characteristics of tail-tremor induced by nicotine in rats.
1994 Aug
5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.
1995 May
The role of brain acetylcholine in phenol-induced tremor in mice.
1995 May
Tacrine interacts with an allosteric activator site on alpha 4 beta 2 nAChRs in M10 cells.
1996 Sep 2
[3H]benzylpempidine, a new radioligand for probing a putative channel site on nicotinic cholinergic receptors.
1997
[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].
1997 Jun
Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.
1997 May
Nicotine potentiates sulpiride-induced catalepsy in mice.
1998
Rat alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor stably expressed in a transfected cell line: pharmacology of ligand binding and function.
1998 Aug
Nicotine prevents experimental parkinsonism in rodents and induces striatal increase of neurotrophic factors.
1998 Dec
Anti-nicotinic properties of anticholinergic antiparkinson drugs.
1998 Nov
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.
1999 Feb 5
Sex differences in cholinergic analgesia II: differing mechanisms in two models of allodynia.
1999 Nov
Chronic nicotine exposure reduces N-methyl-D-aspartate receptor-mediated damage in the hippocampus without altering calcium accumulation or extrusion: evidence of calbindin-D28K overexpression.
2001
Nicotine potentiation of morphine-induced catalepsy in mice.
2002 May
Dizocilpine improves beneficial effects of cholinergic antagonists in anticholinesterase-treated mice.
2003 Apr
Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats.
2003 Apr 11
Decreased prepulse inhibition during nicotine withdrawal in DBA/2J mice is reversed by nicotine self-administration.
2003 Jul 4
GABAergic systems modulate nicotinic receptor-mediated seizures in mice.
2003 Sep
Nicotine-induced antinociception, rewarding effects, and physical dependence are decreased in mice lacking the preproenkephalin gene.
2005 Feb 2
Nicotine attenuates beta-amyloid-induced neurotoxicity by regulating metal homeostasis.
2006 Jun
The nicotinic receptor antagonists abolish pathobiologic effects of tobacco-derived nitrosamines on BEP2D cells.
2006 Oct
Nicotinic modulation of gene expression in SH-SY5Y neuroblastoma cells.
2006 Oct 20
Protective effects of mecamylamine and atropine against α(4)β(2) nicotinic receptor expression and functional toxicity in paraoxon-treated rats.
2008 Sep
Cardiovascular effect of peripheral injected melittin in normotensive conscious rats: Mediation of the central cholinergic system.
2009 Nov-Dec
Repetitive nicotine exposure leads to a more malignant and metastasis-prone phenotype of SCLC: a molecular insight into the importance of quitting smoking during treatment.
2010 Aug
Nicotinic receptor-mediated reduction in L-DOPA-induced dyskinesias may occur via desensitization.
2010 Jun
Neuronal nicotinic acetylcholine receptors as pharmacotherapeutic targets for the treatment of alcohol use disorders.
2010 Mar
Activation and inhibition of mouse muscle and neuronal nicotinic acetylcholine receptors expressed in Xenopus oocytes.
2010 May
ACSL6 is associated with the number of cigarettes smoked and its expression is altered by chronic nicotine exposure.
2011
Association of the histidine-triad nucleotide-binding protein-1 (HINT1) gene variants with nicotine dependence.
2011 Aug
Ryanodine receptor-2 upregulation and nicotine-mediated plasticity.
2011 Jan 5
Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.
2011 Oct 27
Neurotoxicity induced by okadaic acid in the human neuroblastoma SH-SY5Y line can be differentially prevented by α7 and β2* nicotinic stimulation.
2011 Sep
Gestational exposure of mice to secondhand cigarette smoke causes bronchopulmonary dysplasia blocked by the nicotinic receptor antagonist mecamylamine.
2013 Aug
The effects of nicotine and tobacco particulate matter on dopamine uptake in the rat brain.
2014 Feb
Prenatal nicotinic exposure upregulates pulmonary C-fiber NK1R expression to prolong pulmonary C-fiber-mediated apneic response.
2016 Jan 1
Patents

Patents

Sample Use Guides

Usual Adult Dose for Hypertension 2.5 mg orally twice a day; may increase by one 2.5 mg tablet at intervals of 2 days or more until desired blood pressure response is achieved. Comments: -The average total daily dose is 25 mg, usually in 3 divided doses; however, 2.5 mg daily may be sufficient. Partial tolerance may develop in certain patients, which requires an increase in the total daily dose. -Four or more doses may be required when smooth control is difficult to obtain. -Titration should be determined by blood pressure readings in the erect position at the time of maximal effect of this drug, as well as by signs and symptoms of orthostatic hypotension. In severe or urgent cases, titration at larger increments and shorter intervals may be needed.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment:: Racemic mecamylamine and its stereoisomers were tested for their ability to inhibit the ACh-evoked responses of a4b2, a3b4, a3b2, and a7 type receptors expressed in Xenopus oocytes.
10 uM of either mecamylamine stereoisomer produced significant inhibition of the nAChR subtypes.
Name Type Language
MECAMYLAMINE
INN   MI   VANDF   WHO-DD  
INN  
Official Name English
MECAMYLAMINE [INN]
Common Name English
MECAMYLAMINE [WHO-DD]
Common Name English
BICYCLO(2.2.1)HEPTAN-2-AMINE, N,2,3,3-TETRAMETHYL-
Systematic Name English
MECAMYLAMINE [VANDF]
Common Name English
N,2,3,3-TETRAMETHYL-2-NORBORNANAMINE
Systematic Name English
(1RS,2SR,4SR)-N,2,3,3-TETRAMETHYLBICYCLO(2.2.1)HEPTAN-2-AMINE
Systematic Name English
MECAMYLAMINE [MI]
Common Name English
Classification Tree Code System Code
WHO-ATC C02BB01
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
NCI_THESAURUS C66886
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
NDF-RT N0000175641
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
FDA ORPHAN DRUG 117598
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
EPA PESTICIDE CODE 600090
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
LIVERTOX 585
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
NDF-RT N0000175644
Created by admin on Sat Jun 26 11:03:35 UTC 2021 , Edited by admin on Sat Jun 26 11:03:35 UTC 2021
WHO-VATC QC02BB01
Created by admin on Sat Jun 26 11:03:35 UTC 2021 , Edited by admin on Sat Jun 26 11:03:35 UTC 2021
Code System Code Type Description
INN
542
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
CAS
6147-18-8
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
CAS
60-40-2
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
NON-SPECIFIC STEREOCHEMISTRY
DRUG BANK
DB00657
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
FDA UNII
6EE945D3OK
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
RXCUI
6673
Created by admin on Sat Jun 26 11:03:35 UTC 2021 , Edited by admin on Sat Jun 26 11:03:35 UTC 2021
PRIMARY RxNorm
EVMPD
SUB08670MIG
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
IUPHAR
3990
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
WIKIPEDIA
MECAMYLAMINE
Created by admin on Sat Jun 26 11:03:35 UTC 2021 , Edited by admin on Sat Jun 26 11:03:35 UTC 2021
PRIMARY
DRUG CENTRAL
1646
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
EPA CompTox
60-40-2
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
NCI_THESAURUS
C66063
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
MESH
D008464
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
MERCK INDEX
M7113
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
200-476-1
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY
ChEMBL
CHEMBL267936
Created by admin on Sat Jun 26 11:03:34 UTC 2021 , Edited by admin on Sat Jun 26 11:03:34 UTC 2021
PRIMARY