Observations on the Clinical Effects of a new Tranquillizing Agent in Psychotic Conditions

Abstract

The value of the phenothiazine derivative chlorpromazine which was introduced into clinical psychiatry about five years ago has now been well established. Various other phenothiazine derivatives have since been studied systematically in the search for new compounds of potential clinical usefulness. One of these is perphenazine.** Promising results with a group of geriatric patients have recently been reported with this drug. (1) ChemistryPerphenazine is an amino derivative of chlorphenothiazine designated as:It is a white crystalline solid, soluble in organic and inorganic acids. Pharmacology (2, 3) Based on the lethal dose, perphenazine is somewhat less toxic than chlorpromazine. LD so of perphenazine by the intravenous route for mice is 37 mgm/kgm, for the rat 38 mgm/kgm, and for the dog 51 mgm/kgm. Corresponding LD so for chlorpromazine are 28, 28, and 30, respectively. Both chlorpromazine and perphenazine in toxic doses administered intravenously produce death from respiratory arrest with tonic-clonic convulsions.Perphenazine possesses considerable local anaesthetic activity in the guinea pig. It also produces irritation of the tissues when injected subcutaneously or mtramuscularly. The irritation is equivalent to that produced by chlorpromazine in equal concentration.Perphenazine is an active inhibitor of non-specific cholinesterase. In this respect, perphenazine and chlorpromazine are approximately equal in actIvIty. Perphenazine, however, in contrast to chlorpromazine, is a more potent inhibitor of specific cholinesterase. The physiological or clinical implications of this finding are unknown at the present time.Perphenazine shows slight anticholinergic activity and only very slight antihistaminic effects.The drug is equal to chlorpromazine in potentiating barbiturate anaesthesia in mice. When observing the behaviour of animals under the effects of perphenazine, it was noted that the oral administration of 1 mgm/kgm produced a slight change in behaviour in the mouse, rat, cat, dog, and monkey. Three mgrn/kgm consistently brought about marked depression of behaviour, that is, inhibition of spontaneous activity, and of responsiveness. These effects were less pronounced in the cat than in the other species. The tranquillizing activity of perphenazine is about six times as great as that of chlorpromazine.Perphenazine is also about 7 times as active as chlorpromazine in inhibiting the conditioned avoidance response in the rat without depressing the unconditioned response.In anaesthetized dogs, perphenazine resembles chlorpromazine in producing mild hypotension, transient tachycardia, and slight adrenergic blockade when given in small doses. In larger doses, both drugs produce reversal of epinephrine effect. Both chlorpromazine and perphenazine cause cardiac stimulation and

A Long‐term Study of 12 Hospitalized Psychiatric Patients Treated With Perphenazine

“…She mas very suspicious and agitated, and often threatened to kill herself and her childrei. Perphenazine, 4 mg three timcs daily, was started in…”

The Use of Perphenazine (Trilafon) to Control Anxiety and Agitation in Aged Patients

“…One of the most recent, and most promising, of these new agents is perphenazine, a compound in the phenothiazine series which is five to six times as potent as chlorpromazine and much less toxic (6,7). According to early clinical reports (8)(9)(10)(11)(12)(13)(14) perphenazine (Trilafon'") is an effective and comparatively safe tranquilizer suitable for use in the full range of psychiatric indications, from mild tension and anxiety states through frank psychoses.…”