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
The effect of cholinergic stimulation in the nucleus accumbens on locomotor behavior.
1988 Feb 16
Nicotine-sensitive paresis.
1992 Feb
Characteristics of tail-tremor induced by nicotine in rats.
1994 Aug
5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.
1995 May
[Assessment of anti-tremorogenic drugs--nicotine-induced tail-tremor model].
1997 Jun
Nicotine potentiates sulpiride-induced catalepsy in mice.
1998
Pharmacological characterization of nicotine-induced seizures in mice.
1999 Dec
Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant.
1999 Feb 5
A nicotine antagonist, mecamylamine, reduces cue-induced cocaine craving in cocaine-dependent subjects.
1999 Mar
Sex differences in cholinergic analgesia II: differing mechanisms in two models of allodynia.
1999 Nov
Analgesic and toxic effects of ABT-594 resemble epibatidine and nicotine in rats.
2000 Apr
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
Mecamylamine effects on haloperidol-induced catalepsy and defecation.
2001 Jul
Nicotine induced seizures blocked by mecamylamine and its stereoisomers.
2001 Oct 19
Mecamylamine (Inversine): an old antihypertensive with new research directions.
2002 Jul
DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer.
2002 Jun
Nicotine potentiation of morphine-induced catalepsy in mice.
2002 May
Are neuronal nicotinic receptors a target for antiepileptic drug development? Studies in different seizure models in mice and rats.
2003 Apr 11
Nicotine modulates the expression of a diverse set of genes in the neuronal SH-SY5Y cell line.
2003 May 2
GABAergic systems modulate nicotinic receptor-mediated seizures in mice.
2003 Sep
Decreased signs of nicotine withdrawal in mice null for the beta4 nicotinic acetylcholine receptor subunit.
2004 Nov 10
The nicotinic receptor antagonists abolish pathobiologic effects of tobacco-derived nitrosamines on BEP2D cells.
2006 Oct
The involvement of the central cholinergic system in the pressor and bradycardic effects of centrally administrated melittin in normotensive conscious rats.
2007 Apr
Nicotine-induced dystonic arousal complex in a mouse line harboring a human autosomal-dominant nocturnal frontal lobe epilepsy mutation.
2007 Sep 19
Differential role of nicotinic acetylcholine receptor subunits in physical and affective nicotine withdrawal signs.
2008 Apr
Mecamylamine prevents neuronal apoptosis induced by glutamate and low potassium via differential anticholinergic-independent mechanisms.
2008 Mar
Receptor-mediated tobacco toxicity: acceleration of sequential expression of alpha5 and alpha7 nicotinic receptor subunits in oral keratinocytes exposed to cigarette smoke.
2008 May
The limbic circuitry underlying cocaine seeking encompasses the PPTg/LDT.
2009 Oct
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
Discovery of isoxazole analogues of sazetidine-A as selective α4β2-nicotinic acetylcholine receptor partial agonists for the treatment of depression.
2011 Oct 27
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