Procyclidine is also sometimes used for the treatment ofdystonia (but nottardive dyskinesia), a rare disorder that causes abnormal muscle contraction, resulting in twisting postures of limbs, trunk, or face.
Signs of procyclidine overdose are those of ananticholinergic 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 withphysostigmine administered intravenously or subcutaneously.
Procyclidine, 1-cyclohexyl-1-phenyl-3-pyrrolidinopropan-1-ol, is synthesized in exactly the same manner as was seen fortrihexyphenidyl, except this time the linear synthesis begins with the preparation of 3-(1-pyrrolidino)propiophenone.
In an interesting variation, the ketone is first reacted with phenylmagnesium bromide.Catalytic hydrogenation of thecarbinol thus obtained can be stopped after the reduction of only one aromatic ring.
Procyclidine synthesis (Morton)
Morton method:[5][6] 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,PC12565684 (3). The reduction of the ester gives 1-cyclohexyl-1-phenylpropane-1,3-diol,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.
^abcLakstygal AM, Kolesnikova TO, Khatsko SL, Zabegalov KN, Volgin AD, Demin KA, Shevyrin VA, Wappler-Guzzetta EA, Kalueff AV (May 2019). "DARK Classics in Chemical Neuroscience: Atropine, Scopolamine, and Other Anticholinergic Deliriant Hallucinogens".ACS Chem Neurosci.10 (5):2144–2159.doi:10.1021/acschemneuro.8b00615.PMID30566832.
^DE 1084734, Jassmann, Edgar & Pfanz, Hermann, "Verfahren zur Herstellung von tertiäeren Aminoalkoholen [Process for the preparation of tertiary amino alcohols]", published 1960-07-07, assigned to VEB Fahlberg-List Chemische und Pharmazeutische Fabriken
^Adamson DW, Barrett PA, Wilkinson S (1951). "11. Aminoalkyl tertiary carbinols and derived products. Part IV. Spasmolytics. Phenyl- and cyclohexylphenyl-carbinols".Journal of the Chemical Society (Resumed): 52.doi:10.1039/jr9510000052.
^Harfenist Morton, Ernest G Magnien,U.S. patent 2,842,115 (1958 to Burroughs Wellcome Co).
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