Details
Stereochemistry | RACEMIC |
Molecular Formula | C19H29NO |
Molecular Weight | 287.4397 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(CCN1CCCC1)(C2CCCCC2)C3=CC=CC=C3
InChI
InChIKey=WYDUSKDSKCASEF-UHFFFAOYSA-N
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
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
Targets
Primary Target | Pharmacology | Condition | Potency |
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Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2253700 |
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Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1426023 |
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Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2253700 |
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Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2253700 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | KEMADRIN Approved UseKEMADRIN (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 Date1955 |
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Primary | KEMADRIN Approved UseKEMADRIN (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 Date1955 |
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Primary | KEMADRIN Approved UseKEMADRIN (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 Date1955 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
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116 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987788 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2007 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987788 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987788 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987788 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/3987788 |
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
Dose | Population | Adverse events |
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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: |
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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... |
15 mg single, oral Highest studied dose |
unhealthy n = 13 Health Status: unhealthy Condition: Schizophrenia Population Size: 13 Sources: |
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250 mg single, oral Highest studied dose|Studied dose |
unhealthy n = 9 Health Status: unhealthy Condition: duodenal ulcer Population Size: 9 Sources: |
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50 mg single, intramuscular Dose: 50 mg Route: intramuscular Route: single Dose: 50 mg Sources: |
unhealthy n = 3 |
AEs
AE | Significance | Dose | Population |
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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: |
PubMed
Title | Date | PubMed |
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A controlled trial of anti-Parkinson drugs in drug-induced Parkinsonism. | 1966 Jun |
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Drug-induced extrapyramidal symptoms: their incidence and treatment. | 1967 Jan |
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Double-blind comparison of levodopa and procyclidine in parkinsonism, with illustrations of levodopa-induced movement disorders. | 1970 Dec |
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Double-blind comparison of levodopa and procyclidine in parkinsonism, with illustrations of levodopa-induced movement disorders. | 1970 Dec |
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Central role of solar information flow in pregenetic evolution. | 1971 Jun |
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Parenteral long-acting phenothiazines. | 1972 Mar 25 |
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Letter: Delayed drug-induced dystonias. | 1973 Oct 20 |
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Abnormal involuntary movements induced by anticholinergic therapy. | 1974 |
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A comparison of piribedil, procyclidine and placebo in the control of phenothiazine-induced parkinsonism. | 1977 Jun |
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Death attributed to ventricular arrhythmia induced by thioridazine in combination with a single Contac C capsule. | 1978 Oct 7 |
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Sleep disturbance associated with fluphenazine HCl: a case report. | 1979 Jul |
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Ethopropazine and benztropine in neuroleptic-induced parkinsonism. | 1979 Mar |
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Fluphenazine enanthate and fluphenazine decanoate in the treatment of schizophrenic outpatients: extrapyramidal symptoms and therapeutic effect. | 1982 Mar |
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Toxic neurological reaction to lithium/thioridazine. | 1983 Apr 2 |
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Neuroleptic malignant syndrome. | 1983 Jun 18 |
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Effects of mianserin in neuroleptic-induced parkinsonism. | 1986 |
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Rapid cycling following antidepressant in an adolescent. | 1990 May 15 |
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Antipsychotic drug-induced dysphoria. | 1996 Oct |
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Bilateral ulnar nerve paralysis: an unreported complication of drug-induced extrapyramidal rigidity. | 1997 Jun |
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Anti-nicotinic properties of anticholinergic antiparkinson drugs. | 1998 Nov |
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An extrapyramidal reaction to ondansetron. | 1998 Oct |
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Effects of combinational prophylactics composed of physostigmine and procyclidine on soman-induced lethality, seizures and brain injuries. | 2002 Jan |
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Efficacy of immediate and subsequent therapies against soman-induced seizures and lethality in rats. | 2006 Feb |
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Abdominal pain with rigidity secondary to the anti-emetic drug metoclopramide. | 2006 May |
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Pharmacological therapies against soman-induced seizures in rats 30 min following onset and anticonvulsant impact. | 2006 Oct 24 |
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The combination of donepezil and procyclidine protects against soman-induced seizures in rats. | 2007 Apr 15 |
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Low dose quetiapine induced galactorrhoea: a case report. | 2007 Jul 24 |
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An overview of the clinical use of ondansetron in preschool age children. | 2007 Jun |
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Simultaneous prescribing of atypical antipsychotics, conventional antipsychotics and anticholinergics-a European study. | 2007 Jun |
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Newer antipsychotics and the rabbit syndrome. | 2007 Jun 11 |
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Measurements with fluorescent probes in primary neural cultures; improved multiwell techniques. | 2007 Nov-Dec |
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Clozapine and co-prescribed psychotropics: a short report. | 2008 Apr 25 |
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Stuttering priapism--a review of the therapeutic options. | 2008 Aug |
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Anticonvulsant efficacy of drugs with cholinergic and/or glutamatergic antagonism microinfused into area tempestas of rats exposed to soman. | 2008 Feb |
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The present approaches to the development of prophylactic and therapeutic antidotes against nerve agents. | 2008 Jun |
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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 |
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Antiparkinson drugs used as prophylactics for nerve agents: studies of cognitive side effects in rats. | 2008 Jun |
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Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. | 2008 Oct |
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Fatalities associated with clozapine-related constipation and bowel obstruction: a literature review and two case reports. | 2009 Jul-Aug |
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Physiological and pathological role of alpha-synuclein in Parkinson's disease through iron mediated oxidative stress; the role of a putative iron-responsive element. | 2009 Mar |
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Selective T-type calcium channel blockade alleviates hyperalgesia in ob/ob mice. | 2009 Nov |
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Acute dystonic reactions in a lady presenting with repetitive involuntary muscle twitching: a case report. | 2009 Nov 9 |
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Development of a list of potentially inappropriate drugs for the korean elderly using the delphi method. | 2010 Dec |
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Identification of neuronal target areas for nerve agents and specification of receptors for pharmacological treatment. | 2010 Dec |
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Roles of perirhinal and posterior piriform cortices in control and generation of seizures: a microinfusion study in rats exposed to soman. | 2010 Jan |
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The use of organotypic hippocampal slice cultures to evaluate protection by non-competitive NMDA receptor antagonists against excitotoxicity. | 2010 Mar |
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Ethanol extract of Angelica gigas inhibits croton oil-induced inflammation by suppressing the cyclooxygenase - prostaglandin pathway. | 2010 Mar |
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Structured relaxation in the treatment of akathisia: case series. | 2010 May 25 |
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Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
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Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility. | 2013 Dec 15 |
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
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WHO-VATC |
QN04AA04
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NDF-RT |
N0000175370
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NCI_THESAURUS |
C29704
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N04AA04
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N0000175574
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PROCYCLIDINE
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2276
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C73270
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201-023-0
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169103
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m9151
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100000081116
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CHEMBL86715
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56172-67-9
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7280
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DB00387
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)