Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2016 Publisher: Aspen Pharma Trading Limited, 3016 Lake Drive, Citywest Business Campus, Dublin 24, Ireland
Pharmacotherapeutic group: Anticholinergic group
ATC code: N04AA04
Procyclidine is a synthetic anticholinergic agent which blocks the excitatory effects of acetylcholine at the muscarinic receptor.
Idiopathic Parkinson’s disease is thought to result from degeneration of neurones in the substantia nigra whose axons project and inhibit cells in the corpus striatum. Blockade by neuroleptic drugs of the dopamine released by these terminals produces a similar clinical picture. The cell bodies in the corpus striatum also receive cholinergic innervation which is excitatory.
Relief of the Parkinsonian syndrome can be achieved, either by potentiation of the dopaminergic system or blockade of the cholinergic input by anticholinergics. It is by a central action of this latter type by which procyclidine exerts its effect.
Procyclidine is particularly effective in the alleviation of rigidity. Tremor, akinesia, speech and writing difficulties, gait, sialorrhoea and drooling, sweating, oculogyric crises and depressed mood are also beneficially influenced.
Procyclidine is adequately absorbed from the gastro-intestinal tract with a bioavailability of 75% and disappears rapidly from the tissues. The relatively low clearance of 68 ml/min represents a predominantly metabolic change with a small first pass effect. The mean plasma elimination half-life after both oral and intravenous administration is approximately 12hours.
No detailed information is available on the metabolic fate of procyclidine but very little of the parent compound is excreted in the urine unchanged. When given orally about one fifth of the dose is known to be metabolised in the liver, principally by cytochrome P450 and then conjugated with glucuronic acid. This conjugate has been detected in the urine.
A three generation study in rats dosed at 40 mg/kg/day via the diet before and during pregnancy showed only that the number of viable pups was slightly decreased from the second mating. No other parameters were affected.
No teratogenic effects were seen in rats dosed subcutaneously with 10, 30 or 100 mg/kg/day on days 8 to 16 of pregnancy. Maternal bodyweight gain was reduced at doses of 30 or 100 mg/kg/day, and a 10% reduction in foetal weight was seen at 100 mg/kg/day.
Procyclidine was not genotoxic in in vitro bacterial mutation or mouse lymphoma assays.
There are no data on the carcinogenic potential of procyclidine hydrochloride.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
