Summary: A muscarinic antagonist that crosses the blood-brain barrier and is used in the treatment of drug-induced extrapyramidal disorders and in parkinsonism.

Top Publications

  1. Zachariah E, Kumari V, Galea A, Das M, Mehrotra R, Taylor D, et al. Effects of oral procyclidine administration on cognitive functions in healthy subjects: implications for schizophrenia. J Clin Psychopharmacol. 2002;22:224-6 pubmed
  2. Cho Y, Kim W, Hur G, Ha Y. Minimum effective drug concentrations of a transdermal patch system containing procyclidine and physostigmine for prophylaxis against soman poisoning in rhesus monkeys. Environ Toxicol Pharmacol. 2012;33:1-8 pubmed publisher
    A transdermal patch system containing procyclidine, an N-methyl-d-aspartate receptor antagonist possessing anticholinergic action, and physostigmine, a reversible cholinesterase inhibitor, was developed, and its prophylactic efficacy ..
  3. Choi E, Park D, Yon J, Hur G, Ha Y, Che J, et al. Protection by sustained release of physostigmine and procyclidine of soman poisoning in rats. Eur J Pharmacol. 2004;505:83-91 pubmed
    ..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 ..
  4. Ettinger U, Kumari V, Zachariah E, Galea A, Crawford T, Corr P, et al. Effects of procyclidine on eye movements in schizophrenia. Neuropsychopharmacology. 2003;28:2199-208 pubmed
    ..This study investigates effects on eye movements of procyclidine, an anticholinergic drug often administered to schizophrenic patients...
  5. Jevtovic Todorovic V, Meyenburg A, Olney J, Wozniak D. Anti-parkinsonian agents procyclidine and ethopropazine alleviate thermal hyperalgesia in neuropathic rats. Neuropharmacology. 2003;44:739-48 pubmed
    b>Procyclidine and ethopropazine, widely used as anti-parkinsonian agents because of their anti-cholinergic action, are also known to have NMDA antagonist properties...
  6. Kohli Kumar M, Pearson A, Sharkey I, Craft A. Urinary retention--an unusual dystonic reaction to continuous metoclopramide infusion. DICP. 1991;25:469-70 pubmed
    ..This was reversed by procyclidine, suggesting that it may have been a dystonic reaction.
  7. Dinan T, Clarke G, Quigley E, Scott L, Shanahan F, Cryan J, et al. Enhanced cholinergic-mediated increase in the pro-inflammatory cytokine IL-6 in irritable bowel syndrome: role of muscarinic receptors. Am J Gastroenterol. 2008;103:2570-6 pubmed publisher
    ..IBS, depressed patients, and healthy subjects underwent the pyridostigmine test on two separate occasions with procyclidine (antimuscarinic) pre-treatment on one test occasion. Both GH and IL-6 were monitored...
  8. Ring A, Tanso R. Measurements with fluorescent probes in primary neural cultures; improved multiwell techniques. J Pharmacol Toxicol Methods. 2007;56:300-7 pubmed
    ..It has advantages to cuvette techniques because cells have intact dendritic tree and synaptic function and it is a convenient method to obtain reliable dose-response curves for NMDA channel modulators on differentiated neural cells. ..
  9. Myhrer T, Enger S, Aas P. Pharmacological therapies against soman-induced seizures in rats 30 min following onset and anticonvulsant impact. Eur J Pharmacol. 2006;548:83-9 pubmed
    ..modulators muscimol, ethanol, and propofol (screened by micro-infusions) when each drug was combined with procyclidine and administered systemically...

More Information


  1. Dinan T. Neuroleptic effects on platelet aggregation: a study in normal volunteers and schizophrenics. Psychol Med. 1987;17:875-81 pubmed
    ..After 4 weeks of treatment responses tended to return to normal. Aggregation responses were normal in those patients on long-term depot neuroleptics. ..
  2. King D, Burke M, Lucas R. Antipsychotic drug-induced dysphoria. Br J Psychiatry. 1995;167:480-2 pubmed
    ..All adverse effects were transient and were abolished in nine of the ten subjects given procyclidine. While dysphoria is a well-recognized reaction in healthy volunteers, it is probably insufficiently recognised ..
  3. Humphreys A, Tanner A. Acute dystonic drug reaction or tetanus? An unusual consequence of a 'Whizz' overdose. Hum Exp Toxicol. 1994;13:311-2 pubmed
    ..A prolonged period of ventilation may be necessary, but, in this case, complete recovery eventually occurred. ..
  4. Myhrer T, Mariussen E, Enger S, Aas P. Capacities of metabotropic glutamate modulators in counteracting soman-induced seizures in rats. Eur J Pharmacol. 2013;718:253-60 pubmed publisher
    ..combinations with HI-6 (1-[([4-(aminocarbonyl)pyridino]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) and procyclidine or HI-6 and levetiracetam relative to the combination of HI-6, procyclidine, and levetiracetam...
  5. Myhrer T, Enger S, Aas P. The perirhinal cortex of rats: an intricate area for microinfusion of anticonvulsants against soman-induced seizures. Neurotoxicology. 2013;34:128-34 pubmed publisher
    ..against soman intoxication than the use of 1 cannula only in rats infused with the ionotropic antagonists procyclidine and caramiphen or the metabotropic glutamate modulators DCG-IV and MPEP...
  6. Muneer A, Minhas S, Arya M, Ralph D. Stuttering priapism--a review of the therapeutic options. Int J Clin Pract. 2008;62:1265-70 pubmed publisher
    ..Stuttering or recurrent priapism is less well understood. This subtype is characterised by short-lived painful erections and is commonly encountered in patients with sickle cell disease...
  7. Myhrer T, Enger S, Aas P. Cognitive side effects in rats caused by pharmacological agents used to prevent soman-induced lethality. Eur J Pharmacol. 2004;483:271-9 pubmed
    ..The purpose of the present study was to examine whether physostigmine, scopolamine, and various doses of procyclidine might reduce rats' innate preference for novelty...
  8. Nilvebrant L, Sparf B. Receptor binding profiles of some selective muscarinic antagonists. Eur J Pharmacol. 1988;151:83-96 pubmed
    The binding of hexahydrosiladifenidol, procyclidine, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine) and AF-DX 116 to muscarinic receptors in the heart, ileum, urinary bladder, parotid gland and cerebral cortex from guinea pig was studied ..
  9. Martin D, Swash M. Muscle pathology in the neuroleptic malignant syndrome. J Neurol. 1987;235:120-1 pubmed
  10. Spivak B, Gonen N, Mester R, Averbuch E, Adlersberg S, Weizman A. Neuroleptic malignant syndrome associated with abrupt withdrawal of anticholinergic agents. Int Clin Psychopharmacol. 1996;11:207-9 pubmed
    ..NMS appeared following combined neuroleptic/ anticholinergic withdrawal and responded to procyclidine administration...
  11. Myhrer T, Enger S, Aas P. Efficacy of immediate and subsequent therapies against soman-induced seizures and lethality in rats. Basic Clin Pharmacol Toxicol. 2006;98:184-91 pubmed
    ..seizures induced by 3 or 4 x LD(50) of soman could not be terminated unless an adjunct therapy consisting of procyclidine (6 mg/kg), diazepam (10 mg/kg), and pentobarbital (30 kg/kg) was given, and the mortality rate was ..
  12. Hadidi K. Development of a screening method for the most commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine and biperiden. Leg Med (Tokyo). 2004;6:233-41 pubmed
    ..for the simultaneous determination of three commonly abused anticholinergic drugs in Jordan; trihexyphenidyl, procyclidine, and biperiden in plasma and urine has been developed using solid phase extraction and GC-MS...
  13. Kumari V, Zachariah E, Galea A, Jones H, Das M, Mehrotra R, et al. Effects of acute procyclidine administration on prepulse inhibition of the startle response in schizophrenia: a double-blind, placebo-controlled study. J Psychopharmacol. 2003;17:89-95 pubmed
    ..This study determined the effects of procyclidine, an anticholinergic drug, on PPI in patients with schizophrenia given risperidone or quetiapine and not on any ..
  14. Perenyi A, Goswami U, Frecska E, Majláth E, Barcs G, Kassay Farkas A. A pilot study of the role of prophylactic antiparkinson treatment during neuroleptic therapy. Pharmacopsychiatry. 1989;22:108-10 pubmed
    ..Ten patients did not receive anything else (group HPL), while ten patients received procyclidine 5 mg t.i.d., and 13 patients were given promethazine 25 mg t.i.d...
  15. Khan N, Razzak J. Abdominal pain with rigidity secondary to the anti-emetic drug metoclopramide. J Emerg Med. 2006;30:411-3 pubmed
    ..This case report illustrates the importance of considering medication side-effects when evaluating a patient with abdominal pain and rigidity. ..
  16. Joosen M, van der Schans M, Kuijpers W, van Helden H, Noort D. Timing of decontamination and treatment in case of percutaneous VX poisoning: a mini review. Chem Biol Interact. 2013;203:149-53 pubmed publisher what extent a subchronic pretreatment with carbamate (pyridostigmine or physostigmine combined with either procyclidine or scopolamine) would protect against percutaneous VX exposure...
  17. Myhrer T, Nguyen N, Andersen J, Aas P. Protection against soman-induced seizures in rats: relationship among doses of prophylactics, soman, and adjuncts. Toxicol Appl Pharmacol. 2004;196:327-36 pubmed
    The combined effects of physostigmine and procyclidine (antagonizing muscarinic, nicotinic, and NMDA receptors) were tested against various doses of soman. Physostigmine (0...
  18. Haug K, Myhrer T, Fonnum F. The combination of donepezil and procyclidine protects against soman-induced seizures in rats. Toxicol Appl Pharmacol. 2007;220:156-63 pubmed
    ..inhibitor of acetylcholinesterase (AChE) clinically used for treating Alzheimer's disease, in combination with procyclidine, used in treatment of Parkinson's disease and schizophrenia, as prophylaxis against intoxication by the nerve ..
  19. Kumari V, Ettinger U, Crawford T, Zachariah E, Sharma T. Lack of association between prepulse inhibition and antisaccadic deficits in chronic schizophrenia: implications for identification of schizophrenia endophenotypes. J Psychiatr Res. 2005;39:227-40 pubmed
    ..It is concluded that PPI and antisaccade abnormalities in schizophrenia represent separate endophenotypes, reflecting the functions of different genetic aetiologies and different or only partially overlapping neural systems. ..
  20. Kumari V, Zachariah E, Galea A, Mehrotra R, Taylor D, Sharma T. Effects of procyclidine on prepulse inhibition of the acoustic startle response in healthy human volunteers. Psychopharmacology (Berl). 2001;154:221-9 pubmed
    ..This study determined the effects of procyclidine, an anticholinergic drug, on PPI in healthy male volunteers, employing a double-blind placebo-controlled cross-..
  21. Roesler R, Quevedo J, Schroder N. NMDA receptors might be involved in the impairing effects of procyclidine on cognition. J Clin Psychopharmacol. 2003;23:666-7; author reply 667-8 pubmed
  22. Myhrer T, Enger S, Aas P. Roles of perirhinal and posterior piriform cortices in control and generation of seizures: a microinfusion study in rats exposed to soman. Neurotoxicology. 2010;31:147-53 pubmed publisher
    ..scopolamine), glutamatergic antagonism (ketamine, NBQX), both cholinergic and glutamatergic antagonism (procyclidine, caramiphen), or GABAergic agonism (muscimol)...
  23. Myhrer T, Enger S, Jonassen M, Aas P. Enhanced efficacy of anticonvulsants when combined with levetiracetam in soman-exposed rats. Neurotoxicology. 2011;32:923-30 pubmed publisher
    ..brain sites (area tempestas, medial septum, perirhinal cortex, posterior piriform cortex) have shown that procyclidine, muscimol, caramiphen, and NBQX, but not ketamine, exert anticonvulsant effects against soman-induced seizures...
  24. Balzan M. Paradoxical autonomic response to procyclidine in the neuroleptic malignant syndrome. Can J Neurol Sci. 1995;22:244-6 pubmed
    ..Case Study. High dose intravenous therapy with the anticholinergic drug, procyclidine hydrochloride, temporarily diminished the muscle rigidity and reversed most of the autonomic features in a ..
  25. Waelbroeck M, Camus J, Tastenoy M, Lambrecht G, Mutschler E, Tacke R, et al. Stereoselectivity of procyclidine binding to muscarinic receptor subtypes M1, M2 and M4. Eur J Pharmacol. 1990;189:135-42 pubmed
    The goals of the present study were: (1) to investigate the binding properties of (R)- and (S)-procyclidine and two achiral derivatives of muscarinic M1, M2 and M4 receptor subtypes and (2) to identify the interactions which allow these ..
  26. Jutley R, Mason R. Lessons to be learned: a case study approach. 'Spontaneous' intraperitoneal bladder rupture in a psychiatric patient--with diagnostic difficulties. J R Soc Promot Health. 2001;121:125-7 pubmed
    ..The case also highlights the use of procyclidine, commonly used in patients with psychiatric disorders; urinary retention is a recognised side effect of this ..
  27. Hibbard K, Propst A, Frank D, Wyse J. Fatalities associated with clozapine-related constipation and bowel obstruction: a literature review and two case reports. Psychosomatics. 2009;50:416-9 pubmed publisher
    ..The discussion outlines potential mechanisms and management of clozapine-related constipation. ..
  28. Jimbo M, Yamagishi K, Yamaki T, Nunomura K, Kabayama K, Igarashi Y, et al. Development of a new inhibitor of glucosylceramide synthase. J Biochem. 2000;127:485-91 pubmed
    ..3 microM. In cultured cells, PBPP was able to deplete glycosphingolipids without affecting cell growth or the ceramide level. ..
  29. Alharbi M, Maickel R. Differential effects of central and peripheral cholinergic blockade on water consumption by rats. Pharmacol Res. 1990;22:71-4 pubmed
    ..b>Procyclidine (5 mg/kg, s.c...
  30. Deahl M. Betel nut-induced extrapyramidal syndrome: an unusual drug interaction. Mov Disord. 1989;4:330-2 pubmed
    ..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.
  31. El Haj B, Al Amri A, Ali H. Target urinary analytes for the gas chromatographic- mass spectrometric detection of procyclidine and benzhexol in drug abuse cases. J Anal Toxicol. 2011;35:92-8 pubmed
    The two antiparkinsonian drugs procyclidine and benzhexol are presently finding considerable favor for their euphoric hallucinogenic effects among drug abusers in some countries...
  32. Sharma T, Galea A, Zachariah E, Das M, Taylor D, Ruprah M, et al. Effects of 10 mg and 15 mg oral procyclidine on critical flicker fusion threshold and cardiac functioning in healthy human subjects. J Psychopharmacol. 2002;16:183-7 pubmed
    ..Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in ..
  33. Zhao X, You T, Liu J, Sun X, Yan J, Yang X, et al. Drug-human serum albumin binding studied by capillary electrophoresis with electrochemiluminescence detection. Electrophoresis. 2004;25:3422-6 pubmed
    ..Three basic drugs, namely pridinol, procyclidine and its analogue trihexyphenidyl, were successfully separated by capillary zone electrophoresis with end-column ..
  34. Brown D, Silverstone T, Cookson J. Carbamazepine compared to haloperidol in acute mania. Int Clin Psychopharmacol. 1989;4:229-38 pubmed
    ..No serious haematological changes, nor abnormalities in clinical chemistry occurred in either group. We conclude that CBZ appears to be a potentially useful drug in the treatment of acute mania. ..
  35. Schifano F, Di Costanzo E. Excessive use of anticholinergic drugs in a sub-sample of Italian schizophrenics. Int J Clin Pharmacol Ther Toxicol. 1991;29:184-6 pubmed
    ..Ten point four percent of the sample (22 patients) took these drugs in amounts greater than those prescribed. Some possible explanations of this excessive use are discussed...
  36. Holeman J, Danielson N. Microbore liquid chromatography of tertiary amine anticholinergic pharmaceuticals with tris(2,2'-bipyridine)ruthenium(III) chemiluminescence detection. J Chromatogr Sci. 1995;33:297-302 pubmed
    ..chemiluminescent pH conditions for atropine, scopolamine, dicyclomine, cyclopentolate, cyclobenzaprine, and procyclidine are determined at moderately basic conditions (pH 7 to 9)...
  37. Myhrer T, Enger S, Mariussen E, Aas P. Two medical therapies very effective shortly after high levels of soman poisoning in rats, but only one with universal utility. Toxicology. 2013;314:221-8 pubmed publisher
    ..From these studies procyclidine emerged as the most potent anticonvulsant, and its potency was further enhanced when being combined with the ..
  38. Waelbroeck M, Camus J, Tastenoy M, Mutschler E, Strohmann C, Tacke R, et al. Stereoselective interaction of procyclidine, hexahydro-difenidol, hexbutinol and oxyphencyclimine, and of related antagonists, with four muscarinic receptors. Eur J Pharmacol. 1992;227:33-42 pubmed
    ..the binding properties of the (R)- and (S)-enantiomers of the muscarinic antagonists trihexyphenidyl, procyclidine, hexahydro-difenidol, p-fluoro-hexahydro-difenidol, hexbutinol, p-fluoro-hexbutinol, and their corresponding ..
  39. Myhrer T, Enger S, Aas P. Antiparkinson drugs used as prophylactics for nerve agents: studies of cognitive side effects in rats. Pharmacol Biochem Behav. 2008;89:633-8 pubmed publisher
    ..3 mg/kg), biperiden (0.11 mg/kg), caramiphen (10 mg/kg), procyclidine (3 mg/kg), and trihexyphenidyl (0.12 mg/kg) separately and each in combination with physostigmine (0.1 mg/kg)...
  40. Rogiers V, Paeme G, Sonck W, Vercruysse A. Metabolism of procyclidine in isolated rat hepatocytes. Xenobiotica. 1987;17:849-57 pubmed
    1. The biotransformation of procyclidine in isolated hepatocytes, prepared from untreated and from phenobarbital-pretreated rats, is described. 2...
  41. King H, Corry P, Wauchob T, Barclay P. Probable dystonic reaction after a single dose of cyclizine in a patient with a history of encephalitis. Anaesthesia. 2003;58:257-60 pubmed
    ..A presumptive diagnosis of a dystonic reaction to cyclizine was made. She received two doses of procyclidine before her symptoms completely resolved...
  42. Schjelderup L, Harbitz O, Groth P, Aasen A. Syntheses of (S)-(+)-trihexyphenidyl hydrochloride and (S)-(+)-procyclidine hydrochloride, two anticholinergics, using (S)-(-)-3-cyclohexyl-3-hydroxy-3-phenylpropanoic acid as chiral synthon. Acta Chem Scand B. 1987;41:356-61 pubmed
    ..of the anticholinergic trihexyphenidyl hydrochloride has been established as (R) by syntheses of (S)-(+)-procyclidine hydrochloride, whose absolute configuration has been established previously, and (S)-(+)-trihexyphenidyl ..
  43. Buhrich N, Weller A, Kevans P. Misuse of anticholinergic drugs by people with serious mental illness. Psychiatr Serv. 2000;51:928-9 pubmed
    ..Marginalized patients living in the community are vulnerable to the misuse of anticholinergic drugs...
  44. Thornton A, McKenna P. Acute dystonic reactions complicated by psychotic phenomena. Br J Psychiatry. 1994;164:115-8 pubmed
    ..The similarity of these states to the complex neuropsychiatric disturbances seen in post-encephalitic Parkinsonism is emphasised. ..
  45. Owen J, Sribney M, Lawson J, Delva N, Letemendia F. Capillary gas chromatography of trihexyphenidyl, procyclidine and cycrimine in biological fluids. J Chromatogr. 1989;494:135-42 pubmed
    A sensitive (50-100 pg/ml) method is described for the analysis of the anticholinergic drugs cycrimine, procyclidine and trihexyphenidyl by capillary gas chromatography with flame thermionic detection...
  46. Kim W, Cho Y, Kim J, Huang Z, Park S, Choi E, et al. Protection by a transdermal patch containing physostigmine and procyclidine of soman poisoning in dogs. Eur J Pharmacol. 2005;525:135-42 pubmed
    The prophylactic efficacy of a combinational patch system containing physostigmine and procyclidine against soman intoxication was evaluated using dogs...
  47. Myhrer T, Enger S, Aas P. Behavioral side effects in rats treated with acetylcholinesterase inhibitors suggested used as prophylactics against nerve agents. Pharmacol Biochem Behav. 2010;95:338-43 pubmed publisher
    ..5mg/kg), and donepezil (2.5mg/kg) alone or each drug in combination with anticholinergic procyclidine (3mg/kg)...
  48. Senechal A, Landry P, Deschamps R, Lessard M. [Neutropenia in a patient treated with clozapine in combination with other psychotropic drugs]. Encephale. 2002;28:567-9 pubmed
    ..The patient was also taking haloperidol (4 mg/day), methotrimeprazine (35 mg/day), procyclidine (5 mg/day) and valproic acid (1,500 mg/day)...
  49. Jang E, Lee Y, Chung S, Shim C. Nasal absorption of procyclidine in rats and dogs. Arch Pharm Res. 2001;24:219-23 pubmed
    Nasal absorption of procyclidine, a synthetic anticholinergic compound, was investigated in Wistar rats and Beagle dogs. The dosing solution was prepared by dissolving 14C-procyclidine in 50% ethanolic saline...
  50. Zarnowski T, Kleinrok Z, Turski W, Czuczwar S. The NMDA antagonist procyclidine, but not ifenprodil, enhances the protective efficacy of common antiepileptics against maximal electroshock-induced seizures in mice. J Neural Transm Gen Sect. 1994;97:1-12 pubmed
    b>Procyclidine (up to 20 mg/kg i.p...