CHLORPROTHIXENE AND AMTTRIPTYLINEt: INTERACTION WITH THIOPENTONE, CIRCULATORY EFFECT AND ANTISIALOGOGUE EFFECT

Abstract

Evaluation of the interaction of chlorprothixene and amitriptyline with thiopentone, in dogs, showed that both of these have pharmacological properties which cause delayed recovery from anaesthesia. This effect is particularly strong with chlorprothixene. The effect on the circulatory response to tilt was measured with these two drugs in young healthy male subjects, and both caused orthostatic hypotension, which was rather severe in the case of chlorprothixene, and mild with amitriptyline. Tests of antisialogogue activity with chlorprothixene, on the same subjects, showed that this drug was inactive in this respect, although it is reported to exert very strong anticholinergic effects on other organ systems. Chlorprothixene and amitriptyline have some pharmacological properties that led to the suggestion that they might be of value in pre-anaesthetic medication. Chlorprothixene is the transisomer of 2-chloro-9-(3-dimethylaminopropylidene thioxanthene, which is closely related to the phenothiazine derivative chlorpromazine-the main difference being the substitution of carbon for nitrogen in the central ring. Their pharmacological properties are quite similar (Pellmont et al., 1960). Amitriptyline is a cyclic dibenzyl compound which resembles imipramine (Tofranil) in chemical structure, the difference being the same as in the above comparison. The latter two also have similar properties (fig. 1) (Vernier, 1961; Scheckel, 1963). Prior to considering clinical evaluation of these two for pre-anaesthetic medication, we wished to define clearly a few of their pharmacological properties, as reported here.