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Chemical Compound Review

Trilafon     2-[4-[3-(2- chlorophenothiazin-10...

Synonyms: Decentan, Emesinal, Fentazin, Trifaron, Trilifan, ...
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Disease relevance of perphenazine

  • Perphenazine, 1 mg i.m. daily, a dose known to cause hyperprolactinemia, also impaired the efficacy of A-43818 [1].
  • MTW9-P, an ovariectomy-responsive tumor developed in rats maintained on daily perphenazine injections, had 4-fold-higher prolactin binding than had MTW9MtT, an ovariectomy-nonresponsive tumor developed in rats bearing the mammosomatotropic pituitary tumor, MtTW10 [2].
  • We describe a patient who we suspect had perphenazine-induced lupus erythematosus with CAC [3].
  • A 51 year old woman sustained ventricular fibrillation while receiving perphenazine and protriptyline [4].
  • In the lactating rats, there was striking mucosal hyperplasia of both jejunum and ileum but, despite the hyperprolactinaemia, there were no such changes in villus height, crypt depth, or in mucosal wet weight, protein, or DNA/unit length intestine in the perphenazine-injected or pituitary-transplanted animals [5].

Psychiatry related information on perphenazine

  • This report presents results of a double-blind, randomized, placebo-controlled clinical trial designed to evaluate the combination of perphenazine and amitriptyline hydrochloride with that of perphenazine alone in the treatment of 35 ambulatory chronic schizophrenic patients in whom depressive symptoms developed [6].
  • This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia [7].
  • This was associated with a significant increase in central nervous system side effects of perphenazine, including oversedation, extrapyramidal symptoms, and impairment of psychomotor performance and memory (p < 0.05) [8].
  • The ethers which result from this change have increased lipophilicity compared to their ability to inhibit perphenazine-induced catatonia in rats [9].
  • Improvement in two individual BPRS items (hallucinations and conceptual disorganization) was related to serum perphenazine levels and suggestive of a lower therapeutic threshold of 0.8 ng/mL [10].

High impact information on perphenazine

  • A significant decrease was seen, however, in basal and perphenazine-stimulated levels of prolactin after pregnancy in both the younger and older first-pregnancy groups but not in the controls [11].
  • Importantly, exposure to perphenazine, a compound that induces mammary gland differentiation but does not confer protection, does not induce p53 expression, indicating that p53 is not a differentiation marker [12].
  • Proliferation and differentiation of the mammary gland does not explain this phenomenon, as shown by the relative ineffectiveness of perphenazine, a potent mitogenic and differentiating agent [13].
  • Rats bearing these tumors were randomly assigned to no treatment, 7-day castration, and 7-day castration followed by 1-, 3-, 7-, and 10-day treatment with estradiol benzoate (5 micrograms) and perphenazine (1 mg) to stimulate prolactin release [14].
  • Cytosol estradiol binding was determined in MTW9-MtT, 47.6 +/- 3.6 (N = 9), Kd 9.9 +/- 2.0 X 10(-11) M; MTW9-P, 195.5 +/- 9.1 (n = 16), Kd 27.6 +/- 4.7 X 10(-11) M; MTW9-P after perphenazine was withdrawn, 86.0 +/- 6.0 (n = 6), Kd 9.9 +/- 1.5 X 10(-11) M [15].

Chemical compound and disease context of perphenazine


Biological context of perphenazine


Anatomical context of perphenazine


Associations of perphenazine with other chemical compounds


Gene context of perphenazine


Analytical, diagnostic and therapeutic context of perphenazine


  1. Modification of the effect of a gonadoliberin analog on 7,12-dimethylbenz(a)anthracene-induced rat mammary tumors by hormone replacement. Rose, D.P., Pruitt, B. Cancer Res. (1979) [Pubmed]
  2. Prolactin binding in ovariectomy-responsive and ovariectomy-nonresponsive rat mammary carcinoma. Powell, B.L., Diamond, E.J., Koprak, S., Hollander, V.P. Cancer Res. (1977) [Pubmed]
  3. Phenothiazine-induced systemic lupus erythematosus with superior vena cava syndrome: case report and review of the literature. Steen, V.D., Ramsey-Goldman, R. Arthritis Rheum. (1988) [Pubmed]
  4. Electrophysiologic studies of perphenazine and protriptyline in a patient with psychotropic drug-induced ventricular fibrillation. Magorien, R.D., Jewell, G.M., Schaal, S.F., Leier, C.V. Am. J. Med. (1979) [Pubmed]
  5. Prolactin and the small intestine. Effect of hyperprolactinaemia on mucosal structure in the rat. Muller, E., Dowling, R.H. Gut (1981) [Pubmed]
  6. Treatment of secondary depression in schizophrenia. A double-blind, placebo-controlled trial of amitriptyline added to perphenazine. Prusoff, B.A., Williams, D.H., Weissman, M.M., Astrachan, B.M. Arch. Gen. Psychiatry (1979) [Pubmed]
  7. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Pollock, B.G., Mulsant, B.H., Rosen, J., Sweet, R.A., Mazumdar, S., Bharucha, A., Marin, R., Jacob, N.J., Huber, K.A., Kastango, K.B., Chew, M.L. The American journal of psychiatry. (2002) [Pubmed]
  8. Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo. Ozdemir, V., Naranjo, C.A., Herrmann, N., Reed, K., Sellers, E.M., Kalow, W. Clin. Pharmacol. Ther. (1997) [Pubmed]
  9. Synthesis and preliminary pharmacological activity of aminoalkoxy isosteres of glycolate ester anticholinergics. Fries, D.S., Amdrako, J. J. Med. Chem. (1977) [Pubmed]
  10. The relationship between blood perphenazine levels, early resolution of psychotic symptoms, and side effects. Mazure, C.M., Nelson, J.C., Jatlow, P.I., Kincare, P., Bowers, M.B. The Journal of clinical psychiatry. (1990) [Pubmed]
  11. Long-term effect of a first pregnancy on the secretion of prolactin. Musey, V.C., Collins, D.C., Musey, P.I., Martino-Saltzman, D., Preedy, J.R. N. Engl. J. Med. (1987) [Pubmed]
  12. p53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis. Sivaraman, L., Conneely, O.M., Medina, D., O'Malley, B.W. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  13. Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy. Guzman, R.C., Yang, J., Rajkumar, L., Thordarson, G., Chen, X., Nandi, S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  14. Kinetic and morphometric responses of heterogeneous populations of experimental breast cancer cells in vivo. Lancaster, S., English, H.F., Demers, L.M., Manni, A. Cancer Res. (1988) [Pubmed]
  15. Estradiol binding in ovariectomy-responsive and -nonresponsive rat mammary carcinoma. Diamond, E.J., Giladi, M., Khan, S., Hollander, V.P. Cancer Res. (1977) [Pubmed]
  16. Dynamics of prolactin secretion in patients with hypopituitarism and pituitary macroadenomas. Arafah, B.M., Nekl, K.E., Gold, R.S., Selman, W.R. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  17. Efficacy of the combination of fluoxetine and perphenazine in the treatment of psychotic depression. Rothschild, A.J., Samson, J.A., Bessette, M.P., Carter-Campbell, J.T. The Journal of clinical psychiatry. (1993) [Pubmed]
  18. D1/D2 dopamine and N-methyl-D-aspartate (NMDA) receptor participation in experimental catalepsy in rats. Verma, A., Kulkarni, S.K. Psychopharmacology (Berl.) (1992) [Pubmed]
  19. Preoperative oral antiemetics for reducing postoperative vomiting after tonsillectomy in children: granisetron versus perphenazine. Fujii, Y., Saitoh, Y., Tanaka, H., Hidenori, T. Anesth. Analg. (1999) [Pubmed]
  20. Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. Dahl-Puustinen, M.L., Lidén, A., Alm, C., Nordin, C., Bertilsson, L. Clin. Pharmacol. Ther. (1989) [Pubmed]
  21. The CYP2D6 genotype predicts the oral clearance of the neuroleptic agents perphenazine and zuclopenthixol. Jerling, M., Dahl, M.L., Aberg-Wistedt, A., Liljenberg, B., Landell, N.E., Bertilsson, L., Sjöqvist, F. Clin. Pharmacol. Ther. (1996) [Pubmed]
  22. Perphenazine in breast milk and serum. Olesen, O.V., Bartels, U., Poulsen, J.H. The American journal of psychiatry. (1990) [Pubmed]
  23. Pharmacologic profile of perphenazine's metabolites. Sweet, R.A., Pollock, B.G., Mulsant, B.H., Rosen, J., Sorisio, D., Kirshner, M., Henteleff, R., DeMichele, M.A. Journal of clinical psychopharmacology. (2000) [Pubmed]
  24. High-dose treatment of rats with perphenazine enanthate. Fog, R., Pakkenberg, H., Juul, P., Bock, E., Jorgensen, O.S., Andersen, J. Psychopharmacology (Berl.) (1976) [Pubmed]
  25. Effect of hypothalamic implantation of perphenazine on milk yield in goats. Vandeputte-Van Messom, G., Peeters, G. J. Endocrinol. (1982) [Pubmed]
  26. Predominant role of prolactin in stimulating the growth of 7, 12-dimethylbenz(a)anthracene-induced rat mammary tumor. Manni, A., Trujillo, J.E., Pearson, O.H. Cancer Res. (1977) [Pubmed]
  27. Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report. Reynolds, C.F., Frank, E., Perel, J.M., Imber, S.D., Cornes, C., Morycz, R.K., Mazumdar, S., Miller, M.D., Pollock, B.G., Rifai, A.H. The American journal of psychiatry. (1992) [Pubmed]
  28. Relevance of liver enzyme elevations with four different neuroleptics: a retrospective review of 7,263 treatment courses. Gaertner, I., Altendorf, K., Batra, A., Gaertner, H.J. Journal of clinical psychopharmacology. (2001) [Pubmed]
  29. Cytochrome p450 phenotyping/genotyping in patients receiving antipsychotics: useful aid to prescribing? Dahl, M.L. Clinical pharmacokinetics. (2002) [Pubmed]
  30. Serotonin and dopamine receptor gene polymorphisms and the risk of extrapyramidal side effects in perphenazine-treated schizophrenic patients. Gunes, A., Scordo, M.G., Jaanson, P., Dahl, M.L. Psychopharmacology (Berl.) (2007) [Pubmed]
  31. Use of perphenazine to control cannibalism in DBA/1 mice. Carter, D.B., Kennett, M.J., Franklin, C.L. Comp. Med. (2002) [Pubmed]
  32. Serum, pituitary and urine concentrations of prolactin and growth hormone in eight strains of mice with varying incidence of mammary tumors. Sinha, Y.N., Vlahakis, G., Vanderlaan, W.P. Int. J. Cancer (1979) [Pubmed]
  33. Amoxapine versus amitriptyline combined with perphenazine in the treatment of psychotic depression. Anton, R.F., Burch, E.A. The American journal of psychiatry. (1990) [Pubmed]
  34. Steady-state serum concentrations of the neuroleptic perphenazine in relation to CYP2D6 genetic polymorphism. Linnet, K., Wiborg, O. Clin. Pharmacol. Ther. (1996) [Pubmed]
  35. A prolactin-dependent, metastasising rat mammary carcinoma as a model for endocrine-related tumour dormancy. Wijsman, J.H., Cornelisse, C.J., Keijzer, R., van de Velde, C.J., van Dierendonck, J.H. Br. J. Cancer (1991) [Pubmed]
  36. Prophylaxis for vomiting by children after tonsillectomy: dexamethasone versus perphenazine. Splinter, W., Roberts, D.J. Anesth. Analg. (1997) [Pubmed]
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