(±)-Procyclidine

287.43966

287.44

201-023-0

169103

DTXSID2023515

Crystals from petroleum ether

N04AA04|N - Nervous system

23.5

4.2

Solid

1.057 g/cm3

86 °C

433.5ºC at 760 mmHg

205.7ºC

1.554

Moderately soluble in water, ~ 30 mg/ml

Procyclidine hydrochloride tablets should be stored in tight containers at a temperature less than 40 deg C, preferably between 15 - 30 deg C. /Procyclidine hydrochloride/

1.22X10-7 mm Hg at 25 deg C (est)

Henry's Law constant = 3.56X10-10 atm-cu m/mol at 25 °C (est)

172.6 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

Hydroxyl radical reaction rate constant = 1.19X10-10 cu cm/molec-sec at 25 °C (est)

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

The Approved Drug Products with Therapeutic Equivalence Evaluations List identifies discontinued drug products, incl procyclidine hydrochloride on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Procyclidine hydrochloride/

LD50=60 mg/kg (IV in mice)

Two cases are described of chronic schizophrenic patients maintained on depot neuroleptics, who developed severe extrapyramidal symptoms following a period of heavy betel nut consumption. A mechanism for this effect is proposed based on the pharmacological antagonism of the anticholinergic agent, procyclidine, by the active alkaloid ingredient of the betel, arecoline.|The efficacy of a combinational prophylactic regimen on the lethality, convulsions, and loss of morphological and functional integrities of the brain induced by an organophosphate soman was investigated in rats. The rats were implanted subcutaneously with osmotic minipumps containing the combinational prophylactic regimen composed of physostigmine, a reversible cholinesterase inhibitor, and procyclidine, an N-methyl-D-aspartate antagonist possessing anticholinergic action, for 3 days, and intoxicated subcutaneously with soman (160 ug/kg, 1.3 LD50). The doses of combinational regimen in minipumps were optimized to achieve 30-35% inhibition of blood cholinesterase activity by physostigmine and 50-100 ng/ml of blood concentrations of procyclidine as clinically available doses, respectively. In comparison, 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium (HI-6, 125 mg/kg) was administered intraperitoneally 30 min prior to the soman challenge in control groups to reduce mortality of rats without affecting convulsions. Soman induced profound limbic convulsions and 30% mortality, leading to increased blood-brain barrier permeability, neural injuries, learning and memory impairments, and physical incapacitation of survived rats pretreated with HI-6. The combinational regimen, at optimal doses without adverse effects on passive avoidance performances (72 ug/kg/hr of physostigmine plus 432 ug/kg/hr of procyclidine), exerted full protective effects against lethality, convulsions, blood-brain barrier opening, brain injuries, learning and memory impairments, and physical incapacitation induced by soman. Taken together, it is suggested that the combination of physostigmine and procyclidine, at adequate doses, could be a choice to provide the victims of organophosphate poisoning with chance of intensive care for survival and neuroprotection.|... Significant protective efficacy of donepezil (2.5 mg/kg) combined with procyclidine (3 or 6 mg/kg) /was observed/ when given prophylactically against a lethal dose of soman (1.6 x LD50) in Wistar rats. No neuropathological changes were found in rats treated with this combination 48 hr after soman intoxication. Six hours after soman exposure cerebral AChE activity and acetylcholine (ACh) concentration was 5% and 188% of control, respectively. The ACh concentration had returned to basal levels 24 h after soman intoxication, while AChE activity had recovered to 20% of control. Loss of functioning muscarinic ACh receptors (17%) but not nicotinic receptors was evident at this time point...|The prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against soman intoxication was evaluated using dogs. Female beagle dogs (body weights 9-10 kg) were shaved on the abdominal side, attached with a matrix-type patch (7x7 cm) containing 1.5% of physostigmine plus 6% procyclidine for 2 days, and challenged with subcutaneous injection of serial doses (2-10 LD50) of soman. Separately, in combination with the patch attachment, atropine (2 mg/dog) plus 2-pralidoxime (600 mg/dog) or atropine plus 1-[([4-(aminocarbonyl)pyridinio]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridiniu m (HI-6, 500 mg/dog) were injected intramuscularly 1 min after soman poisoning. The LD50 value of soman was determined to be 9.1 ug/kg, and high doses (> or = 1.4 LD50) of soman induced salivation, emesis, defecation and diarrhea, tremors and seizures, and recumbency of dogs, leading to 100% mortality in 24 hr. The prophylactic patch, which led to mean 18.5-18.8% inhibition of blood cholinesterase activity by physostigmine and mean 7.9-8.3 ng/mL of blood concentration of procyclidine, exerted a high protection ratio (4.7 LD50), in comparison with relatively-low effects of traditional antidotes, atropine plus 2-pralidoxime (2.5 LD50) and atropine plus HI-6 (2.7 LD50). Noteworthy, a synergistic increase in the protection ratio was achieved by the combination of the patch with atropine plus HI-6 (9 LD50), but not with atropine plus 2-pralidoxime (5 LD50). In addition, the patch system markedly attenuated the cholinergic signs and seizures induced by soman, especially when combined with atropine plus HI-6, leading to elimination of brain injuries and physical incapacitation up to 6 LD50 of soman poisoning. Taken together, it is suggested that the patch system containing physostigmine and procyclidine, especially in combination with atropine and HI-6, could be a choice for the quality survival from nerve-agent poisoning.|For more Interactions (Complete) data for PROCYCLIDINE (12 total), please visit the HSDB record page.

LD50 mouse intraperitoneal 131 mg/kg|LD50 mouse intravenous 60 mg/kg

Approximately 100% bound to albumin.

For the treatment of all forms of Parkinson's Disease, as well as control of extrapyramidal reactions induced by antipsychotic agents.

Discontinued ... Kemadrin (procyclidine hydrochloride) tablets will remain available ... until current supplies are deleted. /Procyclidine hydrochloride/|Procyclidine is used for the adjunctive treatment of all forms of parkinsonian syndrome. In the symptomatic treatment of parkinsonian syndrome, procyclidine appears to relieve muscle rigidity better than it does tremor. The drug may be combined with other agents in the treatment of more severe cases of tremor, fatigue, weakness, and sluggishness and in advanced rigidity. Procyclidine is also used for the relief of parkinsonian signs and symptoms of antipsychotic agent-induced (e.g., phenothiazines) extrapyramidal effects.|Clinical reports indicate that procyclidine often successfully relieves the symptoms of extrapyramidal dysfunction (dystonia, dyskinesia, akathisia, and parkinsonism) which accompany the therapy of mental disorders with phenothiazine and rauwolfia compounds. In addition to minimizing the symptoms induced by tranquilizing drugs, the drug effectively controls sialorrhea resulting from neuroleptic medication. At the same time, freedom from the side effects induced by tranquilizer drugs, as provided by the administration of procyclidine, permits a more sustained treatment of the patient's mental disorder.|Clinical results in the treatment of parkinsonism indicate that most patients experience subjective improvement characterized by a feeling of well-being and increased alertness, together with diminished salivation and a marked improvement in muscular coordination as demonstrated by objective tests of manual dexterity and by increased ability to carry out ordinary self-care activities. While the drug exerts a mild atropine-like action and therefore causes mydriasis, this may be kept minimal by careful adjustment of the daily dosage.|For more Therapeutic Uses (Complete) data for PROCYCLIDINE (13 total), please visit the HSDB record page.

... Patients with hypotension receiving therapy with procyclidine should be observed closely. Patients with mental disorders receiving procyclidine for control of drug-induced extrapyramidal effects should also be carefully observed, especially at the beginning of therapy or during dosage adjustment, since worsening of mental symptoms or toxic psychosis can occur.|Procyclidine hydrochloride should not be used in angle-closure glaucoma although simple type glaucomas do not appear to be adversely affected.|Use in Children: Safety and efficacy have not been established in the pediatric age group; therefore, the use of procyclidine hydrochloride in this age group requires that the potential benefits be weighed against the possible hazards to the child.|Pregnancy Warning: The safe use of this drug in pregnancy has not been established; therefore, the use of procyclidine hydrochloride in pregnancy, lactation, or in women of childbearing age requires that the potential benefits be weighed against the possible hazards to the mother and child.|For more Drug Warnings (Complete) data for PROCYCLIDINE (12 total), please visit the HSDB record page.

Procyclidine has an atropine-like action on parasympathetic-innervated peripheral structures including smooth muscle. It's antispasmodic effects are thought to be related to the blockage of central cholinergic receptors M1, M2 and M4. It is used to treat symptomatic Parkinsonism and extrapyramidal dysfunction caused by antipsychotic agents.

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. (See all compounds classified as Antiparkinson Agents.)|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. (See all compounds classified as Muscarinic Antagonists.)

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. ...

After intraperitoneal administration of procyclidine, eight metabolites were isolated from rat urine. They were identified as 1-(4-oxocyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol, 1-(cis-4-hydroxycyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol, 1-(trans-4-hydrocyclohexyl)-1-phenyl-3-(1-pyrrolidinyl)-1-propanol , (1R,3R,4S,7R)- and (1R,3R,4S,7S)-1-(cis-3,cis-4-dihydroxycyclohexyl)-1-phenyl-3-(1-py rrolidinyl)- 1-propanol, (1R,3R,4R,7R)- and (1R,3R,4R,7S)-1-(cis-3,trans-4-dihydroxycyclohexyl)-1-phenyl- 3-(1-pyrrolidinyl)-1-propanol, and one of both (1R,3S,4R,7R)- or (1R,3S,4R,7S)- 1-(trans-3,trans-4-dihydroxycyclohexyl)-1-phenyl-3-(1-pyrrolidinyl )-1-propanol by comparative TLC, GLC-MS and 13C-NMR spectroscopy. PMID:6745301

The pharmacokinetics and pharmacodynamics of procyclidine (10 mg) after oral and intravenous administration were studied in six healthy volunteers. ... Plasma elimination half-life of procyclidine ... was .... 12 hr.

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.|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 ganglion- blocking 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.

/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/

/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.

Arpicolin

Oral: Tablets 5 mg Kemadrin (scored) Monarch (a division of King Pharmaceuticals). /Kemadrin hydrochloride/

Discontinued ... Kemadrin tablets will remain available ... until current supplies are deleted. /Hydrochloride/

Analyte: procyclidine; matrix: solutions; procedure: capillary electrophoresis with ultraviolet detection at 200 and 210 nm|Analyte: procyclidine; matrix: solutions; procedure: capillary electrophoresis with ultraviolet detection at 200 nm|Analyte: procyclidine; matrix: solutions; procedure: high-performance liquid chromatography with electrochemical oxidation detection|Analyte: procyclidine; matrix: solutions; procedure: high-performance liquid chromatography with chemiluminescence detection; limit of detection: 0.1-1 ug/mL

Analyte: procyclidine; matrix: blood (plasma), urine; procedure: gas chromatography with mass spectrometry detection; limit of detection: 0.5 ng/mL|Analyte: procyclidine; matrix: blood, biological fluids; procedure: high-performance liquid chromatography with diode array detection and ultraviolet detection at 229 nm

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Pharmaceuticals