プロシクリジン

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.

/CASE REPORTS/ A case of procyclidine abuse is described in which the clinical presentation was indistinguishable from mania. The patient was a long-standing poly-drug abuser and was obtaining the drugs from medical sources. Controlled exposure on the ward to drugs of abuse, including a double-blind comparison with placebo, confirmed that procyclidine caused a manic response in this patient.

/CASE REPORTS/ ... A 34-year-old woman with a psychiatric disorder ... was referred to the local surgical receiving unit with abdominal pain and vomiting. She remained well and fully mobile but refused blood investigations until the day following admission. At that time the tests showed a picture of acute renal failure. With the development of increasing abdominal tenderness and pyrexia she was persuaded to have a laparotomy which demonstrated a small tear at the dome of the bladder. Her deranged blood biochemistry returned to normal within 11 hr following surgery. The important points demonstrated in this case study are the special clinical difficulties encountered in psychiatric patients, which may consequently lead to delay in diagnosis. This delay allowed significant peritoneal reabsorption of urea and creatinine, which masqueraded as 'acute renal failure' on biochemical testing. The case also highlights the use of procyclidine, commonly used in patients with psychiatric disorders; urinary retention is a recognized side effect of this drug--and it is possible that such retention together with a minor and hence easily overlooked episode of trauma, may have contributed to the patient's condition.

Benchmark Dataset for the Liver Toxicity Knowledge Base (LTKB)

procyclidine

Kemadrin®

Anticholinergics

Not Applicable

no-DILI-concern

/LABORATORY ANIMALS: Acute Exposure/ In dogs, the intraperitoneal administration of procyclidine hydrochloride in doses of 5 mg/kg caused maximal dilation of the pupil and inhibition of salivation, but had no toxic action. When the dose was increased to 20 mg/kg, the same symptoms occurred, and in addition there were tremors and ataxia lasting 4 to 5 hours. In one animal, convulsions occurred which were controlled by pentobarbital. In all animals behavior returned to normal within 24 hours. /Procyclidine hydrochloride/

/LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Chronic toxicity tests in rats showed that the compound caused only a very slight retardation in growth, and no change in the erythrocyte count or the histological appearance of the lungs, liver, spleen, and kidney when as much as 10 mg/kg body weight was given subcutaneously daily for 9 weeks.

/LABORATORY ANIMALS: Neurotoxicity/... The purpose of the present study was to examine whether physostigmine, scopolamine, and various doses of procyclidine might reduce rats' innate preference for novelty. When these drugs were tested separately, the results showed that physostigmine (0.1 mg/kg) and procyclidine (3 mg/kg) did not affect preference for novelty, whereas scopolamine (0.15 mg/kg) and procyclidine in a higher dose (6 mg/kg) resulted in a preference deficit (Experiment 1). In Experiment 2, the combination of physostigmine and scopolamine or physostigmine and procyclidine (6 mg/kg) caused a marked deficit in preference for novelty. A much milder deficit was observed when physostigmine was combined with lower doses (1 or 3 mg/kg) of procyclidine. The latter combinations also had milder adverse impact on the animals' interest in the test environment and activity measures than the former combinations. By combining physostigmine with anticholinergics, a potentiation of adverse effects on behavior was seen. It is concluded that a slight cognitive impairment might be unavoidable with effective prophylactics.

/LABORATORY ANIMALS: Neurotoxicity/ ... This study describes the anti-nicotinic properties of the clinically used anticholinergic antiparkinson drugs, benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl. Nicotine-induced convulsion and arecoline-induced tremor in mice were effectively prevented by these drugs. The concentrations of benztropine, biperiden, caramiphen, ethopropazine, procyclidine and trihexyphenidyl affording 50% prevention of nicotine-induced convulsion (ED50 values) were 7.4, 4.6, 7.8, 4.9, 3.1 and 3.3 mg/kg, respectively...

/LABORATORY ANIMALS: Neurotoxicity/ The behavioral effects of a variety of advanced candidate anticonvulsants for organophosphate-induced seizures were evaluated under two rodent counting models. Rats pressed the left of two levers a number of times (a run) before pressing the right lever. The targeted performance was a run of 12. The training contingency was a targeted percentile schedule, which provided food if the current run was closer to 12 than two-thirds of the most recent runs. Baseline performance was well controlled by the target, with mean run lengths slightly less than 12. Once this performance was acquired, half the subjects were switched to a procedure providing food following runs of different lengths with a probability yoked to previous percentile schedule performance. The two procedures generate comparable baseline performances, but behavioral disruptions generate reinforcement loss only under the yoked procedure. Atropine, scopolamine, azaprophen, aprophen, trihexyphenidyl, procyclidine, benactyzine, biperiden and diazepam were tested. All produced dose-related decreases in overall run length and response rate. Responding was disrupted more readily under the yoked procedure than under the percentile procedure. Only atropine affected responding at doses below those effective against soman-induced seizures. Of the present candidates, trihexyphenidyl, procyclidine, benactyzine and biperiden appear most promising for further development.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

LD50 mouse intraperitoneal 131 mg/kg

LD50 mouse intravenous 60 mg/kg

C6QE1Q1TKR

PROCYCLIDINE

Established Pharmacologic Class [EPC] - Anticholinergic

Mechanisms of Action [MoA] - Cholinergic Antagonists

Procyclidine is an Anticholinergic. The mechanism of action of procyclidine is as a Cholinergic Antagonist.

Agents used in the treatment of Parkinson's disease. The most commonly used drugs act on the dopaminergic system in the striatum and basal ganglia or are centrally acting muscarinic antagonists.

Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system.

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. Treatment order was randomized and the study was placebo-controlled and conducted blind. After oral dosing the mean peak plasma concentration was 116 ng/mL and mean bioavailability was 75%. After both oral and intravenous dosing the mean values for the volume of distribution, total body clearance and plasma elimination half-life of procyclidine were in the order of 1 L/kg, 68 mL/min and 12 hr respectively. ...