Originator
Artane,Lederle,US,1949
Uses
Trihexyphenidyl, an antiparkinsonian drug, possesses central and peripheral anticholinergic actions, as well as a direct relaxant effect on smooth muscle. It reduces muscle rigidity and general stiffness, and has a relatively minor effect on tremors. It is used in
Parkinsonism in the form of monotherapy as well as in combination with levodopa.
Uses
Anticholinergic; antiparkinsonian.
Definition
ChEBI: Trihexyphenidyl is an amine.
Manufacturing Process
Acetophenone, paraformaldehyde and piperidine are first reacted to give ω-(1-
piperidyl)propiophenone.
To an absolute ethyl ether solution of cyclohexylmagnesium bromide
(prepared from 261 parts of cyclohexyl bromide, 38.8 parts magnesium
turnings and 700 parts by volume absolute ethyl ether) a dry solution of 174
parts omega-(1-piperidyl)-propiophenonein 600 parts by volume of ether is
added, with stirring, at such a rate that gentle reflux is maintained with no
external cooling or heating. The reaction mixture is stirred for about 5 hours
and then allowed to stand at room temperature until reaction appears
complete. While being cooled the reaction mixture is then decomposed by the
dropwise addition of 500 parts by volume of 2.5 N hydrochloric acid, and
finally is made strongly acidic to Congo red by the addition of concentrated
hydrochloric acid.
The resulting white solid is collected on a filter, air dried, redissolved in 2,500
parts water at 95°C and the resulting solution treated with decolorizing
charcoal and clarified by filtration. The cooled filtrate is made alkaline with
ammonia and the product, crude 3-(1-piperidyl)-1-cyclohexyl-1-phenyl-1-
propanol is collected. The hydrochloride melts with decomposition in ten
seconds in a bath held at 258.5°C. The alcohol melts at 114.3° to 115.0°C,
according to US Patent 2,716,121.
brand name
Artane (Lederle); Tremin (Schering).
Therapeutic Function
Antiparkinsonian
Safety Profile
Poison by intraperitoneal, subcutaneous, and intravenous routes. When heated to decomposition it emits toxic fumes of NOx.
Synthesis
Trihexyphenidyl, 1-cyclohexyl-1-phenyl-3-piperidineopropan-1-ol
(10.2.2), is synthesized by the reaction of 2-(1-piperidino)propiophenone (10.2.1) with cyclohexylmagnesiumbromide. The initial 2-(1-piperidino)propiophenone is synthesized in turn
by the aminomethylation of benzophenone using paraformaldehyde and piperidine [24¨C27].
