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
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
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 0.6 µM [Ki] | |||
Target ID: CHEMBL1907589 |
2.5 µM [IC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | INVERSINE Approved UseFor the management of moderately severe to severe essential hypertension and in uncomplicated cases of malignant hypertension. Launch Date-4.36665614E11 |
|||
| Primary | Unknown Approved UseUnknown |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
7.89 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
115.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
10.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11354389 |
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
| Dose | Population | Adverse 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%) Sources: 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%) |
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%) Sources: Constipation (4.2%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
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.
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Common Name | English |
| Classification Tree | Code System | Code | ||
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WHO-ATC |
C02BB01
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NCI_THESAURUS |
C66886
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NDF-RT |
N0000175641
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FDA ORPHAN DRUG |
117598
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EPA PESTICIDE CODE |
600090
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LIVERTOX |
585
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NDF-RT |
N0000175644
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WHO-VATC |
QC02BB01
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| Code System | Code | Type | Description | ||
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542
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PRIMARY | |||
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6147-18-8
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PRIMARY | |||
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60-40-2
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NON-SPECIFIC STEREOCHEMISTRY | |||
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DB00657
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PRIMARY | |||
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6EE945D3OK
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PRIMARY | |||
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6673
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PRIMARY | RxNorm | ||
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SUB08670MIG
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PRIMARY | |||
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3990
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PRIMARY | |||
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MECAMYLAMINE
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PRIMARY | |||
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1646
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PRIMARY | |||
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60-40-2
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PRIMARY | |||
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C66063
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PRIMARY | |||
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D008464
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PRIMARY | |||
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M7113
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PRIMARY | Merck Index | ||
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200-476-1
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CHEMBL267936
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PRIMARY |
ACTIVE MOIETY
