Identification

Name
Mecamylamine
Accession Number
DB00657  (APRD00458)
Type
Small Molecule
Groups
Approved, Investigational
Description

A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [PubChem]

Structure
Thumb
Synonyms
  • Versamine
Product Ingredients
IngredientUNIICASInChI Key
Mecamylamine hydrochloride4956DJR58O826-39-1PKVZBNCYEICAQP-UHFFFAOYSA-N
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Mecamylamine HydrochlorideTablet2.5 mg/1OralNexgen Pharma, Inc.2013-03-19Not applicableUs
VecamylTablet2.5 mg/1OralManchester Pharmaceuticals2013-03-19Not applicableUs
VecamylTablet2.5 mg/1OralTuring Pharmaceuticals2013-03-19Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
InversineMecamylamine hydrochloride (2.5 mg/1)TabletOralTargacept, Inc.2006-07-25Not applicableUs
International/Other Brands
Inversine (Targacept)
Categories
UNII
6EE945D3OK
CAS number
60-40-2
Weight
Average: 167.2911
Monoisotopic: 167.167399677
Chemical Formula
C11H21N
InChI Key
IMYZQPCYWPFTAG-UHFFFAOYSA-N
InChI
InChI=1S/C11H21N/c1-10(2)8-5-6-9(7-8)11(10,3)12-4/h8-9,12H,5-7H2,1-4H3
IUPAC Name
N,2,3,3-tetramethylbicyclo[2.2.1]heptan-2-amine
SMILES
CNC1(C)C2CCC(C2)C1(C)C

Pharmacology

Indication

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

Associated Conditions
Pharmacodynamics

Mecamylamine is a potent, oral antihypertensive agent and ganglion blocker, and is a secondary amine. 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 crosses the blood-brain and placental barriers.

Mechanism of action

Mecamylamine is a ganglionic blocker which prevents stimulation of postsynaptic receptors by acetylcholine released from presynaptic nerve endings. The hypotensive effect of Mecamylamine is attributed to reduction in sympathetic tone, vasodilation, and reduced cardiac output, and is primarily postural.

TargetActionsOrganism
ANeuronal acetylcholine receptor subunit alpha-2
antagonist
Human
UNeuronal acetylcholine receptor subunit alpha-7Not AvailableHuman
UNeuronal acetylcholine receptor subunit alpha-4Not AvailableHuman
UNeuronal acetylcholine receptor subunit beta-2Not AvailableHuman
Absorption

Mecamylamine is almost completely absorbed from the gastrointestinal tract

Volume of distribution
Not Available
Protein binding

40%

Metabolism
Not Available
Route of elimination

Mecamylamine is excreted slowly in the urine in the unchanged form. The rate of its renal elimination is influenced markedly by urinary pH. Alkalinization of the urine reduces, and acidification promotes, renal excretion of mecamylamine. Mecamylamine crosses the blood-brain and placental barriers.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with 1,10-Phenanthroline.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe risk or severity of adverse effects can be increased when 5-(2-methylpiperazine-1-sulfonyl)isoquinoline is combined with Mecamylamine.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline may increase the hypotensive activities of Mecamylamine.
AcebutololMecamylamine may increase the hypotensive activities of Acebutolol.
AcemetacinThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with Acemetacin.
AcetaminophenAcetaminophen may decrease the excretion rate of Mecamylamine which could result in a higher serum level.
Acetyl sulfisoxazoleThe risk or severity of adverse effects can be increased when Acetyl sulfisoxazole is combined with Mecamylamine.
Acetylsalicylic acidThe therapeutic efficacy of Mecamylamine can be decreased when used in combination with Acetylsalicylic acid.
AclidiniumMecamylamine may increase the anticholinergic activities of Aclidinium.
AgmatineThe risk or severity of adverse effects can be increased when Mecamylamine is combined with Agmatine.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,831,027.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014795
KEGG Compound
C07511
PubChem Compound
4032
PubChem Substance
46508607
ChemSpider
3892
BindingDB
50061565
ChEBI
6706
ChEMBL
CHEMBL267936
Therapeutic Targets Database
DAP000027
PharmGKB
PA450334
IUPHAR
3990
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mecamylamine
ATC Codes
C02BB01 — Mecamylamine

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentAutistic Disorder / Pervasive Developmental Disorder NOS1
1CompletedTreatmentSmoking1
1RecruitingBasic ScienceHealthy Aging1
1, 2Active Not RecruitingTreatmentChronic Orthostatic Intolerance / Tachycardia1
2CompletedTreatmentAge-Related Macular Degeneration (ARMD)1
2CompletedTreatmentAlcoholism1
2CompletedTreatmentDepression / Major Depressive Disorder (MDD)1
2CompletedTreatmentDepressive Disorders1
2CompletedTreatmentDiabetic Macular Edema (DME)1
2CompletedTreatmentMajor Depressive Disorder (MDD)1
2CompletedTreatmentSmoking1
2TerminatedTreatmentMacular Degeneration1
3CompletedTreatmentAlcohol Dependence / Depression1
Not AvailableCompletedBasic ScienceCognition / Magnetic Resonance Imaging (MRI) / Mecamylamine / Nicotine1
Not AvailableCompletedTreatmentCognition in Schizophrenia1

Pharmacoeconomics

Manufacturers
  • Targacept inc
Packagers
  • Layton Bioscience Inc.
  • Siegfried Ltd.
Dosage forms
FormRouteStrength
TabletOral2.5 mg/1
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
PropertyValueSource
melting point (°C)249 with decompositionU.S. Patent 2,831,027.
boiling point (°C)72 °C at 4.00E+00 mm HgPhysProp
logP2.7Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.124 mg/mLALOGPS
logP3.13ALOGPS
logP2.37ChemAxon
logS-3.1ALOGPS
pKa (Strongest Basic)10.88ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area12.03 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity51.83 m3·mol-1ChemAxon
Polarizability20.74 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9566
Blood Brain Barrier+0.9771
Caco-2 permeable+0.611
P-glycoprotein substrateNon-substrate0.6815
P-glycoprotein inhibitor INon-inhibitor0.8271
P-glycoprotein inhibitor IINon-inhibitor0.889
Renal organic cation transporterNon-inhibitor0.7727
CYP450 2C9 substrateNon-substrate0.7864
CYP450 2D6 substrateNon-substrate0.7207
CYP450 3A4 substrateSubstrate0.5884
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.9054
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.7435
Ames testNon AMES toxic0.9315
CarcinogenicityNon-carcinogens0.8757
BiodegradationNot ready biodegradable0.6954
Rat acute toxicity2.3843 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9676
hERG inhibition (predictor II)Non-inhibitor0.8756
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-014i-0900000000-d1e9fe76d5bc86bef4e9
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001r-9700000000-9505ece9327e31f47ce0
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-9000000000-e4663d1da4e4bc059200
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-9000000000-c6fd00cf5fa5e7d227e5
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-003r-9000000000-e197ecfa004b426aeb2b
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-001r-9500000000-4e031bcaa41c1a77d136

Taxonomy

Description
This compound belongs to the class of organic compounds known as bicyclic monoterpenoids. These are monoterpenoids containing exactly 2 rings, which are fused to each other.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Prenol lipids
Sub Class
Monoterpenoids
Direct Parent
Bicyclic monoterpenoids
Alternative Parents
Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Bicyclic monoterpenoid / Secondary amine / Secondary aliphatic amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound / Amine / Aliphatic homopolycyclic compound
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
primary aliphatic amine (CHEBI:6706)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Drug binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
Gene Name
CHRNA2
Uniprot ID
Q15822
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-2
Molecular Weight
59764.82 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Struthers AM, Wilkinson JL, Dwoskin LP, Crooks PA, Bevins RA: Mecamylamine, dihydro-beta-erythroidine, and dextromethorphan block conditioned responding evoked by the conditional stimulus effects of nicotine. Pharmacol Biochem Behav. 2009 Dec;94(2):319-28. doi: 10.1016/j.pbb.2009.09.012. Epub 2009 Sep 22. [PubMed:19778551]
  5. Shytle RD, Penny E, Silver AA, Goldman J, Sanberg PR: Mecamylamine (Inversine): an old antihypertensive with new research directions. J Hum Hypertens. 2002 Jul;16(7):453-7. [PubMed:12080428]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The cha...
Gene Name
CHRNA7
Uniprot ID
P36544
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-7
Molecular Weight
56448.925 Da
References
  1. Briggs CA, McKenna DG, Monteggia LM, Touma E, Roch JM, Arneric SP, Gopalakrishnan M, Sullivan JP: Gain of function mutation of the alpha7 nicotinic receptor: distinct pharmacology of the human alpha7V274T variant. Eur J Pharmacol. 1999 Feb 5;366(2-3):301-8. [PubMed:10082212]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
noncompetitive antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNA4
Uniprot ID
P43681
Uniprot Name
Neuronal acetylcholine receptor subunit alpha-4
Molecular Weight
69956.47 Da
References
  1. Eaton JB, Peng JH, Schroeder KM, George AA, Fryer JD, Krishnan C, Buhlman L, Kuo YP, Steinlein O, Lukas RJ: Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells. Mol Pharmacol. 2003 Dec;64(6):1283-94. [PubMed:14645658]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Curator comments
noncompetitive antagonist
General Function
Ligand-gated ion channel activity
Specific Function
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeabl...
Gene Name
CHRNB2
Uniprot ID
P17787
Uniprot Name
Neuronal acetylcholine receptor subunit beta-2
Molecular Weight
57018.575 Da
References
  1. Eaton JB, Peng JH, Schroeder KM, George AA, Fryer JD, Krishnan C, Buhlman L, Kuo YP, Steinlein O, Lukas RJ: Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells. Mol Pharmacol. 2003 Dec;64(6):1283-94. [PubMed:14645658]

Drug created on June 13, 2005 07:24 / Updated on August 02, 2018 07:43