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

Details

Stereochemistry RACEMIC
Molecular Formula C19H29NO.ClH
Molecular Weight 323.901
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PROCYCLIDINE HYDROCHLORIDE

SMILES

Cl.OC(CCN1CCCC1)(C2CCCCC2)C3=CC=CC=C3

InChI

InChIKey=ZFSPFXJSEHCTTR-UHFFFAOYSA-N
InChI=1S/C19H29NO.ClH/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;1H

HIDE SMILES / InChI
Procyclidine is a muscarinic antagonist that crosses the blood-brain. Procyclidine hydrochloride (brand name Kemadrin) is a synthetic antispasmodic compound of relatively low toxicity. It has been shown to be useful for the symptomatic treatment of parkinsonism (paralysis agitans) and extrapyramidal dysfunction caused by tranquilizer therapy. Procyclidine hydrochloride was developed at The Wellcome Research Laboratories as the most promising of a series of antiparkinsonism compounds produced by chemical modification of antihistamines. Kemadrin is indicated in the treatment of parkinsonism including the postencephalitic, arteriosclerotic, and idiopathic types. Partial control of the parkinsonism symptoms is the usual therapeutic accomplishment. Procyclidine hydrochloride is usually more efficacious in the relief of rigidity than tremor; but tremor, fatigue, weakness, and sluggishness are frequently beneficially influenced. It can be substituted for all the previous medications in mild and moderate cases. For the control of more severe cases, other drugs may be added to procyclidine therapy as indications warrant. 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. Pharmacologic tests have shown that procyclidine hydrochloride has an atropine-like action and exerts an antispasmodic effect on smooth muscle. It is a potent mydriatic and inhibits salivation. It has no sympathetic ganglionblocking activity in doses as high as 4 mg/kg, as measured by the lack of inhibition of the response of the nictitating membrane to preganglionic electrical stimulation.

CNS Activity

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
KEMADRIN

Approved Use

KEMADRIN (procyclidine hydrochloride) is indicated in the treatment of parkinsonism including the postencephalitic, arteriosclerotic, and idiopathic types. Partial control of the parkinsonism symptoms is the usual therapeutic accomplishment. Procyclidine hydrochloride is usually more efficacious in the relief of rigidity than tremor; but tremor, fatigue, weakness, and sluggishness are frequently beneficially influenced. It can be substituted for all the previous medications in mild and moderate cases. For the control of more severe cases, other drugs may be added to procyclidine therapy as indications warrant.

Launch Date

1955
Primary
KEMADRIN

Approved Use

KEMADRIN (procyclidine hydrochloride) is indicated in the treatment of parkinsonism including the postencephalitic, arteriosclerotic, and idiopathic types. Partial control of the parkinsonism symptoms is the usual therapeutic accomplishment. Procyclidine hydrochloride is usually more efficacious in the relief of rigidity than tremor; but tremor, fatigue, weakness, and sluggishness are frequently beneficially influenced. It can be substituted for all the previous medications in mild and moderate cases. For the control of more severe cases, other drugs may be added to procyclidine therapy as indications warrant.

Launch Date

1955
Primary
KEMADRIN

Approved Use

KEMADRIN (procyclidine hydrochloride) is indicated in the treatment of parkinsonism including the postencephalitic, arteriosclerotic, and idiopathic types. Partial control of the parkinsonism symptoms is the usual therapeutic accomplishment. Procyclidine hydrochloride is usually more efficacious in the relief of rigidity than tremor; but tremor, fatigue, weakness, and sluggishness are frequently beneficially influenced. It can be substituted for all the previous medications in mild and moderate cases. For the control of more severe cases, other drugs may be added to procyclidine therapy as indications warrant.

Launch Date

1955
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
116 ng/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCYCLIDINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2007 ng × h/mL
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCYCLIDINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2705 ng × h/mL
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PROCYCLIDINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.6 h
10 mg single, oral
dose: 10 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
PROCYCLIDINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
11.5 h
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
PROCYCLIDINE HYDROCHLORIDE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
10 mg single, intravenous
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources:
healthy, 22-48 years
n = 6
Health Status: healthy
Age Group: 22-48 years
Sex: M+F
Population Size: 6
Sources:
250 mg single, oral
Overdose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Co-administed with::
amoxapine(2500 mg)
Sources:
unhealthy, 26 years
n = 1
Health Status: unhealthy
Condition: schizo-affective disorder
Age Group: 26 years
Sex: F
Population Size: 1
Sources:
Other AEs: Pancreatitis...
Other AEs:
Pancreatitis (1 patient)
Sources:
15 mg single, oral
Highest studied dose
Dose: 15 mg
Route: oral
Route: single
Dose: 15 mg
Sources:
unhealthy
n = 13
Health Status: unhealthy
Condition: Schizophrenia
Population Size: 13
Sources:
250 mg single, oral
Highest studied dose|Studied dose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Sources:
unhealthy
n = 9
Health Status: unhealthy
Condition: duodenal ulcer
Population Size: 9
Sources:
50 mg single, intramuscular
Dose: 50 mg
Route: intramuscular
Route: single
Dose: 50 mg
Sources:
unhealthy
n = 3
Health Status: unhealthy
Population Size: 3
Sources:
AEs

AEs

AESignificanceDosePopulation
Pancreatitis 1 patient
250 mg single, oral
Overdose
Dose: 250 mg
Route: oral
Route: single
Dose: 250 mg
Co-administed with::
amoxapine(2500 mg)
Sources:
unhealthy, 26 years
n = 1
Health Status: unhealthy
Condition: schizo-affective disorder
Age Group: 26 years
Sex: F
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer
Drug as victim

Drug as victim

PubMed

PubMed

TitleDatePubMed
A controlled trial of anti-Parkinson drugs in drug-induced Parkinsonism.
1966 Jun
Drug-induced extrapyramidal symptoms: their incidence and treatment.
1967 Jan
Central role of solar information flow in pregenetic evolution.
1971 Jun
A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism.
1977 Jun
Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule.
1978 Oct 7
Ethopropazine and benztropine in neuroleptic-induced parkinsonism.
1979 Mar
Effects of mianserin in neuroleptic-induced parkinsonism.
1986
Acute dystonia due to amitriptyline.
1992 May
An extrapyramidal reaction to ondansetron.
1998 Oct
Nasal absorption of procyclidine in rats and dogs.
2001 Jun
Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers.
2001 Mar
Physostigmine as treatment for severe CNS anticholinergic toxicity.
2001 Sep
Effects of oral procyclidine administration on cognitive functions in healthy subjects: implications for schizophrenia.
2002 Apr
Effects of combinational prophylactics composed of physostigmine and procyclidine on soman-induced lethality, seizures and brain injuries.
2002 Jan
NMDA receptors might be involved in the impairing effects of procyclidine on cognition.
2003 Dec
Effects of procyclidine on eye movements in schizophrenia.
2003 Dec
Variable effects of previously untested muscarinic receptor antagonists on experimental myopia.
2003 Mar
Screening and semi-quantitative analysis of post mortem blood for basic drugs using gas chromatography/ion trap mass spectrometry.
2004 Dec 25
Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats.
2004 Nov 28
Development of a screening method for the most commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine and biperiden.
2004 Oct
Soman-induced convulsions in rats terminated with pharmacological agents after 45 min: neuropathology and cognitive performance.
2005 Jan
Protection by a transdermal patch containing physostigmine and procyclidine of soman poisoning in dogs.
2005 Nov 21
Primary care use of antipsychotic drugs: an audit and intervention study.
2005 Nov 29
Abdominal pain with rigidity secondary to the anti-emetic drug metoclopramide.
2006 May
Low dose quetiapine induced galactorrhoea: a case report.
2007 Jul 24
An overview of the clinical use of ondansetron in preschool age children.
2007 Jun
Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study.
2007 Jun
Stuttering priapism--a review of the therapeutic options.
2008 Aug
Amisulpride plus valproate vs haloperidol plus valproate in the treatment of acute mania of bipolar I patients: a multicenter, open-label, randomized, comparative trial.
2008 Jun
Antiparkinson drugs used as prophylactics for nerve agents: studies of cognitive side effects in rats.
2008 Jun
Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors.
2008 Oct
Role of the central cholinergic system in the therapeutics of schizophrenia.
2008 Sep
Mechanisms of action of antipsychotic drugs of different classes, refractoriness to therapeutic effects of classical neuroleptics, and individual variation in sensitivity to their actions: Part II.
2009 Dec
Selective T-type calcium channel blockade alleviates hyperalgesia in ob/ob mice.
2009 Nov
Acute dystonic reactions in a lady presenting with repetitive involuntary muscle twitching: a case report.
2009 Nov 9
Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method.
2010 Dec
Roles of perirhinal and posterior piriform cortices in control and generation of seizures: a microinfusion study in rats exposed to soman.
2010 Jan
Behavioral side effects in rats treated with acetylcholinesterase inhibitors suggested used as prophylactics against nerve agents.
2010 May
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.
2011 Jul 14
Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility.
2013 Dec 15
Patents

Patents

Sample Use Guides

For initial treatment is 2.5 mg administered three times daily after meals. If well tolerated, this dose may be gradually increased to 5 mg three times a day and occasionally 5 mg given before retiring. In some cases smaller doses may be employed with good therapeutic results.
Route of Administration: Oral
In Vitro Use Guide
Unknown
Name Type Language
PROCYCLIDINE HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD  
Common Name English
PROCYCLIDINE HYDROCHLORIDE [MART.]
Common Name English
PROCYCLIDINE HCL
Common Name English
KEMADRIN
Brand Name English
PROCYCLIDINE HYDROCHLORIDE [VANDF]
Common Name English
α-Cyclohexyl-α-phenyl-1-pyrrolidinepropanol hydrochloride
Systematic Name English
PROCYCLIDINE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
1-PYRROLIDINEPROPANOL, .ALPHA.-CYCLOHEXYL-.ALPHA.-PHENYL-, HYDROCHLORIDE
Systematic Name English
PROCYCLIDINE HYDROCHLORIDE [USP-RS]
Common Name English
PROCYCLIDINE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
NSC-757293
Code English
Procyclidine hydrochloride [WHO-DD]
Common Name English
PROCYCLIDINE HYDROCHLORIDE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C38149
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
Code System Code Type Description
ChEMBL
CHEMBL86715
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
MERCK INDEX
m9151
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY Merck Index
FDA UNII
CQC932Z7YW
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
ECHA (EC/EINECS)
216-141-8
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
EVMPD
SUB04054MIG
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
WIKIPEDIA
Procyclidine hydrochloride
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
SMS_ID
100000085102
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
DRUG BANK
DBSALT001008
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PRIMARY
RXCUI
142443
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY RxNorm
PUBCHEM
207841
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PRIMARY
NCI_THESAURUS
C47689
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
NSC
757293
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
EPA CompTox
DTXSID8045357
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY
RS_ITEM_NUM
1567004
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PRIMARY
CAS
1508-76-5
Created by admin on Fri Dec 15 17:14:41 GMT 2023 , Edited by admin on Fri Dec 15 17:14:41 GMT 2023
PRIMARY