{{Short description|Group of stereoisomers}} {{distinguish|Phencyclidine}} {{Drugbox | verifiedrevid = 267631655 | IUPAC_name = 1-cyclohexyl-1-phenyl-3-pyrrolidin-1-yl-propan-1-ol hydrochloride | image = Procyclidine-hydrochloride-2D-skeletal.png | image_class = skin-invert-image <!--Clinical data--> | tradename = | Drugs.com = {{drugs.com|monograph|procyclidine-hydrochloride}} | MedlinePlus = a605037 | pregnancy_category = | legal_status = | routes_of_administration = By mouth, im, iv <!--Pharmacokinetic data--> | bioavailability = | protein_bound = ~100%-albumin | metabolism = | elimination_half-life = ~12 h | excretion = <!--Identifiers--> | CAS_number = 77-37-2 | CAS_supplemental = <br/>77-37-2 (free base) <!-- CAS verified --> | ATC_prefix = N04 | ATC_suffix = AA04 | PubChem = 207841 | DrugBank = DB00387 | ChemSpiderID = 4750 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = C6QE1Q1TKR | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D08425 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 1761 <!--Chemical data--> | C=19 | H=30 | Cl=1 | N=1 | O=1 }}
'''Procyclidine''' is an anticholinergic drug principally used for the treatment of drug-induced parkinsonism, akathisia and acute dystonia, Parkinson's disease, and idiopathic or secondary dystonia.
== Medical uses == It is used in patients with parkinsonism and akathisia, and to reduce the side effects of antipsychotic treatment given for schizophrenia. Procyclidine is also a second-line drug for the treatment of Parkinson's disease. It improves tremor but not rigidity or bradykinesia.
Procyclidine is also sometimes used for the treatment of dystonia (but not tardive dyskinesia), a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.
==Side effects== Side effects include nausea, constipation, urinary retention, blurred vision, anxiety, cognitive impairment, confusion, dizziness, gingivitis, hallucination, memory loss, rash and vomiting. <ref>{{cite web |url=https://bnf.nice.org.uk/drug/procyclidine-hydrochloride.html |title=Procyclidine Hydrochloride |publisher=National Institute for Health and Care Excellence | access-date=2020-07-06}}</ref>
== Overdose == Signs of procyclidine overdose are those of an anticholinergic and include confusion, agitation and sleeplessness that can last up to or more than 24 hours. Pupils become dilated and unreactive to light. Tachycardia (fast heart beat), as well as auditory and visual hallucinations have also been reported.
Other known symptoms of overdose are: clumsiness or unsteadiness, being severely drowsy, having a severely dry mouth, nose, or throat, having an altered mood or other mental changes, seizures, being short of breath or having troubled breathing, a dry and warm, flushed skin.
A suspected overdose with severe life-threatening symptoms should immediately be brought to medical attention, where reversal can be attempted with physostigmine administered intravenously or subcutaneously.
==Pharmacology== ===Pharmacodynamics=== Procyclidine is an anticholinergic.<ref name="LakstygalKolesnikovaKhatsko2019">{{cite journal | vauthors = Lakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV | title = DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens | journal = ACS Chem Neurosci | volume = 10 | issue = 5 | pages = 2144–2159 | date = May 2019 | pmid = 30566832 | doi = 10.1021/acschemneuro.8b00615 | url = }}</ref> It is specifically an antimuscarinic.<ref name="LakstygalKolesnikovaKhatsko2019" /> The drug acts as a non-selective antagonist of the muscarinic acetylcholine M<sub>1</sub>, M<sub>2</sub>, and M<sub>4</sub> receptors, whereas its activities at the M<sub>3</sub> and M<sub>5</sub> receptors are reportedly unknown.<ref name="LakstygalKolesnikovaKhatsko2019" />
==Chemistry== ===Synthesis=== [[File:Procyclidine synthesis.png|class=skin-invert-image|thumb|center|500px|Procyclidine synthesis:<ref>{{Cite patent|country=DE|number=1084734|pubdate=1960-07-07|title=Verfahren zur Herstellung von tertiäeren Aminoalkoholen [Process for the preparation of tertiary amino alcohols]|assign1=VEB Fahlberg-List Chemische und Pharmazeutische Fabriken|inventor1-last=Jassmann|inventor1-first=Edgar|inventor2-last=Pfanz|inventor2-first=Hermann}}</ref> {{US patent|2826590}}]]
Procyclidine, 1-cyclohexyl-1-phenyl-3-pyrrolidinopropan-1-ol, is synthesized in exactly the same manner as was seen for trihexyphenidyl, except this time the linear synthesis begins with the preparation of 3-(1-pyrrolidino)propiophenone.
class=skin-invert-image|thumb|center|400px|Procyclidine synthesis 2<ref>{{cite journal| vauthors = Adamson DW, Barrett PA, Wilkinson S |title=11. Aminoalkyl tertiary carbinols and derived products. Part IV. Spasmolytics. Phenyl- and cyclohexylphenyl-carbinols|journal=Journal of the Chemical Society (Resumed)|year=1951|pages=52|doi=10.1039/jr9510000052}}</ref>
In an interesting variation, the ketone is first reacted with phenylmagnesium bromide. Catalytic hydrogenation of the carbinol thus obtained can be stopped after the reduction of only one aromatic ring.
center|500px|class=skin-invert-image|Procyclidine synthesis (Morton)
Morton method:<ref>Harfenist Morton, Ernest G Magnien, {{US patent|2842115}} (1958 to Burroughs Wellcome Co).</ref><ref>, GB773748 (1957 to Wellcome Foundation Ltd).</ref> The Reformatsky reaction between Cyclohexyl phenyl ketone (BzCy) [712-50-5] ('''1''') and Ethyl Bromoacetate [105-36-2] ('''2''') gives ethyl 3-cyclohexyl-3-hydroxy-3-phenylpropanoate, [https://pubchem.ncbi.nlm.nih.gov/compound/12565684 PC12565684] ('''3'''). The reduction of the ester gives 1-cyclohexyl-1-phenylpropane-1,3-diol, [https://pubchem.ncbi.nlm.nih.gov/compound/13841193 PC13841193] ('''4'''). FGI of the primary alcohol to the Tosyl leaving group gives 3-Cyclohexyl-3-hydroxy-3-phenylpropyl 4-methylbenzenesulfonate [102473-43-8] (5). Alkylation with pyrrolidine [123-75-1] completes the synthesis of procyclidine.
== See also == * Benzatropine * Biperiden * Cycrimine
== References == {{Reflist}}
== Further reading == * {{cite book | title=British National Formulary | edition=45 |date=March 2003| title-link=British National Formulary }}
{{Antiparkinson}} {{Hallucinogens}} {{Muscarinic acetylcholine receptor modulators}}
Category:1-Pyrrolidinyl compounds Category:Hydrochlorides Category:Cyclohexyl compounds Category:M1 receptor antagonists Category:M2 receptor antagonists Category:M3 receptor antagonists Category:M4 receptor antagonists Category:M5 receptor antagonists Category:Tardive dyskinesia Category:Tertiary alcohols