Identification

Name
Procyclidine
Accession Number
DB00387  (APRD00383)
Type
Small Molecule
Groups
Approved
Description

A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism.

Structure
Thumb
Synonyms
  • 1-cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol hydrochloride
  • 1-Cyclohexyl-1-phenyl-3-pyrrolidino-1-propanol
  • Prociclidina
  • Procyclidin
  • Procyclidine
  • Procyclidinum
  • Tricyclamol
Product Ingredients
IngredientUNIICASInChI Key
Procyclidine hydrochlorideCQC932Z7YW1508-76-5ZFSPFXJSEHCTTR-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KemadrinTablet5 mg/1OralMonarch Pharmaceuticals, Inc.1955-05-262008-10-22Us
Kemadrin ElxElixir2.5 mgOralGlaxosmithkline Inc1968-12-312004-08-05Canada
Kemadrin Tab 5mgTablet5 mgOralGlaxosmithkline Inc1956-12-312004-12-02Canada
Procyclid ElxElixir2.5 mgOralIcn Pharmaceuticals1980-12-312005-04-26Canada
Procyclid Tab 5mgTablet5 mgOralIcn Pharmaceuticals1974-12-312005-04-26Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Pdp-procyclidineElixir2.5 mgOralPendopharm Division Of De Pharmascience Inc1984-12-31Not applicableCanada
Pdp-procyclidineTablet2.5 mgOralPendopharm Division Of De Pharmascience Inc1985-12-31Not applicableCanada
Pdp-procyclidineTablet5 mgOralPendopharm Division Of De Pharmascience Inc1985-12-31Not applicableCanada
Pendo-procyclidineTablet2.5 mgOralPendopharm Division Of De Pharmascience IncNot applicableNot applicableCanada
PHL-procyclidine TabletsTablet5 mgOralPharmel Inc1998-02-172010-11-03Canada
PHL-procyclidine TabletsTablet2.5 mgOralPharmel Inc1998-02-172010-11-03Canada
International/Other Brands
Arpicolin (Rosemont) / Extranil (General Pharma) / Kdrine (Opsonin) / Kemadren (GlaxoSmithKline) / Kemadrin (GlaxoSmithKline) / Osnervan (Aspen) / Prodine (Psyco Remedies) / Proimer (Cho Dang)
Categories
UNII
C6QE1Q1TKR
CAS number
77-37-2
Weight
Average: 287.4397
Monoisotopic: 287.224914555
Chemical Formula
C19H29NO
InChI Key
WYDUSKDSKCASEF-UHFFFAOYSA-N
InChI
InChI=1S/C19H29NO/c21-19(17-9-3-1-4-10-17,18-11-5-2-6-12-18)13-16-20-14-7-8-15-20/h1,3-4,9-10,18,21H,2,5-8,11-16H2
IUPAC Name
1-cyclohexyl-1-phenyl-3-(pyrrolidin-1-yl)propan-1-ol
SMILES
OC(CCN1CCCC1)(C1CCCCC1)C1=CC=CC=C1

Pharmacology

Indication

For the treatment of all forms of Parkinson's Disease, as well as control of extrapyramidal reactions induced by antipsychotic agents.

Associated Conditions
Pharmacodynamics

Procyclidine has an atropine-like action on parasympathetic-innervated peripheral structures including smooth muscle. It's antispasmodic effects are thought to be related to the blockage of central cholinergic receptors M1, M2 and M4. It is used to treat symptomatic Parkinsonism and extrapyramidal dysfunction caused by antipsychotic agents.

Mechanism of action

The mechanism of action is unknown. It is thought that Procyclidine acts by blocking central cholinergic receptors, and thus balancing cholinergic and dopaminergic activity in the basal ganglia. Many of its effects are due to its pharmacologic similarities with atropine. Procyclidine exerts an antispasmodic effect on smooth muscle, and may produce mydriasis and reduction in salivation.

TargetActionsOrganism
AMuscarinic acetylcholine receptor M1
antagonist
Human
AMuscarinic acetylcholine receptor M2
antagonist
Human
AMuscarinic acetylcholine receptor M4
antagonist
Human
AMuscarinic acetylcholine receptor M3
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Approximately 100% bound to albumin.

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

LD50=60 mg/kg (IV in mice)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
1,10-PhenanthrolineThe therapeutic efficacy of Procyclidine can be decreased when used in combination with 1,10-Phenanthroline.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-MethoxyamphetamineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with 4-Methoxyamphetamine.
AbediterolThe risk or severity of Tachycardia can be increased when Procyclidine is combined with Abediterol.
AcebutololThe risk or severity of Tachycardia can be increased when Procyclidine is combined with Acebutolol.
AclidiniumThe risk or severity of adverse effects can be increased when Procyclidine is combined with Aclidinium.
AdenosineThe risk or severity of Tachycardia can be increased when Procyclidine is combined with Adenosine.
Food Interactions
Not Available

References

General References
  1. Theodoridis GC, Stark L: Central role of solar information flow in pregenetic evolution. J Theor Biol. 1971 Jun;31(3):377-88. [PubMed:5556140]
External Links
Human Metabolome Database
HMDB0014531
KEGG Drug
D08425
KEGG Compound
C07378
PubChem Compound
4919
PubChem Substance
46505553
ChemSpider
4750
BindingDB
50062598
ChEBI
8448
ChEMBL
CHEMBL86715
Therapeutic Targets Database
DAP001110
PharmGKB
PA164784001
Drugs.com
Drugs.com Drug Page
Wikipedia
Procyclidine
ATC Codes
N04AA04 — Procyclidine
AHFS Codes
  • 28:36.08 — Anticholinergic Agents

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Monarch pharmaceuticals inc
Packagers
Not Available
Dosage forms
FormRouteStrength
TabletOral5 mg/1
ElixirOral2.5 mg
TabletOral2.5 mg
TabletOral5 mg
Prices
Unit descriptionCostUnit
Pms-Procyclidine 2.5 mg Tablet0.06USD tablet
Pms-Procyclidine 0.5 mg/ml Elixir0.03USD ml
Pms-Procyclidine 5 mg Tablet0.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)86 °CPhysProp
water solubilityModerately soluble in water, ~ 30 mg/mlNot Available
logP4.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00984 mg/mLALOGPS
logP4.13ALOGPS
logP3.79ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)13.84ChemAxon
pKa (Strongest Basic)9.45ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area23.47 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity88.6 m3·mol-1ChemAxon
Polarizability34.43 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9822
Blood Brain Barrier+0.9734
Caco-2 permeable+0.6388
P-glycoprotein substrateSubstrate0.6324
P-glycoprotein inhibitor INon-inhibitor0.51
P-glycoprotein inhibitor IINon-inhibitor0.5877
Renal organic cation transporterInhibitor0.7954
CYP450 2C9 substrateNon-substrate0.7956
CYP450 2D6 substrateNon-substrate0.7907
CYP450 3A4 substrateNon-substrate0.5427
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.915
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8682
Ames testNon AMES toxic0.841
CarcinogenicityNon-carcinogens0.9142
BiodegradationNot ready biodegradable0.9178
Rat acute toxicity2.7861 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.6498
hERG inhibition (predictor II)Inhibitor0.5597
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
Mass Spectrum (Electron Ionization)MSsplash10-001i-9010000000-7d7f1b16f54aaca37f10
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as aralkylamines. These are alkylamines in which the alkyl group is substituted at one carbon atom by an aromatic hydrocarbyl group.
Kingdom
Organic compounds
Super Class
Organic nitrogen compounds
Class
Organonitrogen compounds
Sub Class
Amines
Direct Parent
Aralkylamines
Alternative Parents
N-alkylpyrrolidines / Benzene and substituted derivatives / Tertiary alcohols / 1,3-aminoalcohols / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives / Aromatic alcohols
Substituents
Aralkylamine / Monocyclic benzene moiety / Benzenoid / N-alkylpyrrolidine / 1,3-aminoalcohol / Pyrrolidine / Tertiary alcohol / Tertiary aliphatic amine / Tertiary amine / Azacycle
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary alcohol, pyrrolidines (CHEBI:8448)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Phosphatidylinositol phospholipase c activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM1
Uniprot ID
P11229
Uniprot Name
Muscarinic acetylcholine receptor M1
Molecular Weight
51420.375 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. Larson EW, Pfenning MA, Richelson E: Selectivity of antimuscarinic compounds for muscarinic receptors of human brain and heart. Psychopharmacology (Berl). 1991;103(2):162-5. [PubMed:2027917]
  4. Waelbroeck M, Camus J, Tastenoy M, Lambrecht G, Mutschler E, Tacke R, Christophe J: Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4. Eur J Pharmacol. 1990 Sep 18;189(2-3):135-42. [PubMed:2253700]
  5. Myhrer T: Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment. Neurotoxicology. 2010 Dec;31(6):629-38. doi: 10.1016/j.neuro.2010.07.002. Epub 2010 Jul 17. [PubMed:20624420]
  6. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Schjelderup L, Aasen A, Lambrecht G, Christophe J: Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42. [PubMed:1426023]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
G-protein coupled acetylcholine receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM2
Uniprot ID
P08172
Uniprot Name
Muscarinic acetylcholine receptor M2
Molecular Weight
51714.605 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. Larson EW, Pfenning MA, Richelson E: Selectivity of antimuscarinic compounds for muscarinic receptors of human brain and heart. Psychopharmacology (Berl). 1991;103(2):162-5. [PubMed:2027917]
  4. Waelbroeck M, Camus J, Tastenoy M, Lambrecht G, Mutschler E, Tacke R, Christophe J: Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4. Eur J Pharmacol. 1990 Sep 18;189(2-3):135-42. [PubMed:2253700]
  5. Myhrer T: Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment. Neurotoxicology. 2010 Dec;31(6):629-38. doi: 10.1016/j.neuro.2010.07.002. Epub 2010 Jul 17. [PubMed:20624420]
  6. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Schjelderup L, Aasen A, Lambrecht G, Christophe J: Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42. [PubMed:1426023]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Guanyl-nucleotide exchange factor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM4
Uniprot ID
P08173
Uniprot Name
Muscarinic acetylcholine receptor M4
Molecular Weight
53048.65 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. Waelbroeck M, Camus J, Tastenoy M, Lambrecht G, Mutschler E, Tacke R, Christophe J: Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4. Eur J Pharmacol. 1990 Sep 18;189(2-3):135-42. [PubMed:2253700]
  4. Alberts P: Classification of the presynaptic muscarinic receptor subtype that regulates 3H-acetylcholine secretion in the guinea pig urinary bladder in vitro. J Pharmacol Exp Ther. 1995 Jul;274(1):458-68. [PubMed:7616431]
  5. Myhrer T: Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment. Neurotoxicology. 2010 Dec;31(6):629-38. doi: 10.1016/j.neuro.2010.07.002. Epub 2010 Jul 17. [PubMed:20624420]
  6. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Schjelderup L, Aasen A, Lambrecht G, Christophe J: Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42. [PubMed:1426023]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Receptor activity
Specific Function
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the...
Gene Name
CHRM3
Uniprot ID
P20309
Uniprot Name
Muscarinic acetylcholine receptor M3
Molecular Weight
66127.445 Da
References
  1. Myhrer T: Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment. Neurotoxicology. 2010 Dec;31(6):629-38. doi: 10.1016/j.neuro.2010.07.002. Epub 2010 Jul 17. [PubMed:20624420]
  2. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, Schjelderup L, Aasen A, Lambrecht G, Christophe J: Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992 Sep 1;227(1):33-42. [PubMed:1426023]

Drug created on June 13, 2005 07:24 / Updated on December 18, 2018 09:07