Perphenazine effects

Coley KC, Carter CS, DaPos SV, et al (1999). Effectiveness of antipsychotic therapy in a naturalistic setting a comparison between risperidone, perphenazine, and haloperidol./ Clin Psychiatry 60, 850-6. 

Johansen C., Kandel D., Bonese K. The effect of perphenazine on self-administration behavior. Pharmacol. Biochem. Behav. 4 427, 1976. 

Akathisia, Parkinson-like syndrome, galactorrhea, and amenorrhea are side effects of perphenazine, caused by... 

The answer is c. (Hardman, pp 414-4163) Unwanted pharmacologic side effects produced by phenothiazine antipsychotic drugs (e.g., perphenazine) include Parkinson-like syndrome, akathisia, dystonias, galactorrhea, amenorrhea, and infertility. These side effects are due to the ability of these agents to block dopamine receptors. The phenothiazines also block muscarinic and a-adrenergic receptors, which are responsible for other effects. 

Effects similar to those of the neuroleptics have also been described for other dopamine-blocking agents. Thus, parkinsonism and tardive symptoms may result from use of metoclopramide, a drug which is commonly used to enhance gastric motility, or certain antiemetics, such as perphenazine. 

Serious side-effects have been associated with the important psychotherapeutic agent, chlorpromazine (358), almost since its introduction. High sensitivity to sunburn, pigmentation of the skin and ocular opacity are common phototoxic effects [ 196]. In a series of phenothiazines, the chloro-substituted compounds, particularly chlorpromazine, prochlorperazine and perphenazine, showed by far the greatest phototoxic activity [197, 198]. 

Perphenazine (Trilafon). Perphenazine has a potency and side effect profile similar to other medium potency antipsychotics. 

The piperazines include fluphenazine, trifluoperazine, prochlorperazine, perazine and perphenazine. They are agents with a high antipsychotic potency with less pronounced anticholinergic effects. However their potential to produce extrapyramidal effects is more pronounced. 

Eisenberg, L., Gilbert, A., Cytryn, L., and Moiling, PA. (1961) The effectiveness of psychotherapy alone and in conjunction with perphenazine or placebo in the treatment of neurotic and hyperkinetic children. Am J Psychiatry 117 1088-1093. 

Perphenazine is now only available in oral formulation. It is used less and less in anaesthetic practice, usually given with premedication (2-4 mg, 1-2 h pre-operatively). The anti-emetic effects are well recognised but there may be marked sedation. It has a role in anxiety states and in the management of psychiatric cases. 

Three subfamilies of phenothiazines, based primarily on the side chain of the molecule, were once the most widely used of the antipsychotic agents. Aliphatic derivatives (eg, chlorpromazine ) and piperidine derivatives (eg, thioridazine ) are the least potent. These drugs produce more sedation and weight gain. Piperazine derivatives are more potent (effective in lower doses) but not necessarily more efficacious. Perphenazine, a piperazine derivative, was the typical antipsychotic drug used in the CATIE study described in the following text. The piperazine derivatives are also more selective in their pharmacologic effects (Table 29-1). 

Recently, a large study in the USA (CATIE) reported that perphenazine was as effective as atypical antipsychotic drugs, with the modest exception of olanzapine, and concluded that typical antipsychotic drugs are the treatment of choice for schizophrenia based on their lower cost. However, this study did not adequately consider the risk of tardivedyskinesia or the treatment history of patients in the design of this study. 

Recent studies on multidrug reversal in mouse lymphoma and MDR/COLO 320 cells have shown that phenothiazine derivatives, namely perphenazine (2) and prochlorperazine dimaleate (4), effectively inhibited rhodamine efflux [171]. Other phenothiazine derivatives such as promethazine (1), ox-omemazine (20), methotrimeprazine maleate (18), triflupromazine (11), and trimeprazine (17) differently modulated intracellular rhodamine accumulation in these resistant cells. The effect of some substitution in the phenothiazine ring was studied in mouse lymphoma cells expressing P-gp [172], The 3,7,8-trihydroxy- and 7,8-dihydroxychlorpromazine derivatives were effective P-gp inhibitors, whereas 7,8-diacetoxy-, 7,8-dimethoxy-, 7-semicarbazone-, and 5-oxo-chlorpromazine derivatives exerted only a moderate effect. 

In the phenothiazine series of neuroleptics, thioridazine has less antimuscarinic potency than chlorpromazine, but appears to be equally active as an antagonist of 5-HT2 and D2 receptors like chlorpromazine, however, it is a potent alpha] adrenoceptor antagonist. In contrast, the potent phenothiazine neuroleptic perphenazine is only slightly less selective in blocking D2 receptors than haloperidol but, unlike the latter, has a greater antagonistic effect on histamine receptors. 

Figure 3. The effects of dietary fat on perphenazine stimulated prolactin release in female rats after 18 weeks of feeding.

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