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Procyclidine

N04A - Anticholinergic agents ATC N04AA04 Small molecule approved 1955 Oral Natural product

JFDA label: Kemadrin Tablets

Mechanism of Action

Thought to act by blocking excess acetylcholine at cerebral synapses; many of its effects are due to its pharmacologic similarities with atropine; it exerts an antispasmodic effect on smooth muscle, is a potent mydriatic; inhibits salivation

Indications

Approved

  • Extrapyramidal side effects
  • Parkinson disease

Contraindications

Source: Lexicomp

  • Angle-closure glaucoma Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (1)

Not Known Dizziness

Immune system disorders (1)

Not Known Hypersensitivity reaction

Gastrointestinal disorders (5)

Not Known Constipation · epigastric distress · nausea · vomiting · xerostomia

Skin and subcutaneous tissue disorders (1)

Not Known Skin rash

Musculoskeletal and connective tissue disorders (1)

Not Known Weakness

Eye disorders (2)

Not Known Blurred vision · mydriasis

Dosing

Source: Lexicomp

Parkinson disease: Oral: Initial: 2.5 mg 3 times daily after meals; if tolerated, gradually increase to 5 mg 3 times daily after meals and 5 mg at bedtime as needed. Lower dosages may be effective in some patients; if bedtime dose is not tolerated, may omit and administer total daily dose in 3 equally divided daytime doses Conversion from alternative therapy: Gradually initiate procyclidine 2.5 mg 3 times daily (may be used to replace all or part of alternative therapy); titrate dosage up (procyclidine) and/or down (alternative therapy) until satisfactory effect is achieved with procyclidine monotherapy Extrapyramidal side effects: Oral: Initial: 2.5 mg 3 times daily after meals; increase in 2.5 mg daily increments until symptomatic relief; usual dose: 10 to 20 mg daily in divided doses
Refer to adult dosing; use with caution and at the lowest dose possible
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Warnings & Precautions

Source: Lexicomp

Anhidrosis/hyperthermia

Anticholinergic agents may cause anhidrosis and hyperthermia, which may be severe; use with caution in hot weather or during exercise. The risk is increased in hot environments, particularly in the elderly, alcoholics, patients with CNS disease, and those with prolonged outdoor exposure.

CNS effects

May be associated with restlessness, confusion, hallucinations, or other CNS effects, particularly in the elderly and generally at higher dosages; intensification of symptoms or toxic psychosis may occur in patients with mental disorders. Dose reductions/discontinuation of therapy may be necessary. May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Disease-related concerns:

Cardiovascular disease

Use with caution in patients with tachycardia, cardiac arrhythmias, hypertension, or hypotension.

GI obstruction

Use with caution in patients with obstructive disease of the GI.

Hepatic impairment

Use with caution in patients with hepatic impairment.

Prostatic hyperplasia/urinary stricture

Use with caution in patients with prostatic hyperplasia and/or urinary stricture or retention.

Renal impairment

Use with caution in patients with renal impairment. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly

Frequently develop increased sensitivity and require strict dosage regulation - side effects may be more severe in elderly patients with atherosclerotic changes.

Pregnancy & Lactation

Pregnancy

Safe use during pregnancy or in women considering pregnancy has not been established.

Lactation

It is not known if procyclidine is excreted in breast milk

Monitoring

Clinical pearlSymptoms of EPS or Parkinson's disease, pulse, anticholinergic effects (ie, CNS, bowel and bladder function)

Chemistry & Properties

2D structure
FormulaC19H29NO
Molecular weight287.45 g/mol
IUPAC name1-cyclohexyl-1-phenyl-3-pyrrolidin-1-ylpropan-1-ol
CAS77-37-2
PubChem CID4919
InChIKeyWYDUSKDSKCASEF-UHFFFAOYSA-N
logP3.94 (XLogP 4.1)
Polar surface area23.47 Ų
H-bond acceptors / donors2 / 1
Drug-likeness (QED)0.89
Lipinski violations0
SMILESOC(CCN1CCCC1)(c1ccccc1)C1CCCCC1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrantYes

Enzyme interactions

EnzymeRoleDetail
CYP2B6Inhibitor
CYP2D6Inhibitor
CYP2D6Substrate
CYP3A4Substrate

Receptor binding (top 5)

TargetActionAffinity
Cholinergic, muscarinic M1 (CHRM1) Binding pKi 8.3
Cholinergic, muscarinic M4 (CHRM4) Binding pKi 8.2
Cholinergic, muscarinic M3 (CHRM3) Binding pKi 7.9
Cholinergic, muscarinic M5 (CHRM5) Binding pKi 7.6
Cholinergic, muscarinic M2 (CHRM2) Binding pKi 7.6

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OCT2 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (70, DDInter)

Interacting drugSeverityManagement
Potassium chloride major
Potassium citrate major
Aclidinium moderate
Acrivastine moderate
Alimemazine moderate
Atropine moderate
Azatadine moderate
Brimonidine (ophthalmic) moderate
Brimonidine (topical) moderate
Brompheniramine moderate
Carbinoxamine moderate
Cetirizine moderate
Chlorcyclizine moderate
Chlorphenesin moderate
Chlorpheniramine moderate
Clemastine moderate
Clidinium moderate
Clofedanol moderate
Codeine moderate
Cyclizine moderate
Cyproheptadine moderate
Dexbrompheniramine moderate
Dextromethorphan moderate
Dicyclomine moderate
Diphenhydramine moderate
Doxepin moderate
Doxepin (topical) moderate
Doxylamine moderate
Dronabinol moderate
Edrophonium moderate
Eluxadoline moderate
Ethanol moderate
Glycopyrronium moderate
Glycopyrronium (topical) moderate
Hydrocodone moderate
Hyoscyamine moderate
Ipratropium moderate
Ketoconazole moderate
Levocetirizine moderate
Loperamide moderate

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Registered Products (2)

BrandForm / strengthPackAgentCitizen (JOD)
Kemadrin Tablets Tablet 5 mg 100 tab Suleiman Tannous & Sons Co. Ltd 4.490
Kemadrin Ampoules Ampoule 10 mg/2 ml 2 ml Suleiman Tannous & Sons Co. Ltd 6.690