Abstract
This study was designed to examine the hypothesis that phenelzine is metabolized by polymorphic acetylation and that its effects are dependent on acetylator status. 30 depressed inpatients were given a 3-week course of phenelzine 30 mg t.i.d. The antidepressant effect, the degree of inhibition of monoamine oxidase and the amount of free phenelzine excreted in the urine were all significantly greater in slow acetylators than in fast. These findings strongly support the hypothesis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aitken, R. C. B.: Measurement of feelings using visual analogue scales. Proc. roy. Soc. Med. 62, 989–993 (1969)
Caddy, B., Johnstone, Eve C., Tilstone, W. J.: Unpublished work. (To be submitted to Brit. J. clin. Pharmacol.)
Carney, M. W. P., Roth, M., Garside, R. F.: The diagnosis of depressive symptoms and the prediction of ECT response. Brit. J. Psychiat. 111, 659–674 (1965)
Clinical Psychiatry Committee Report to Medical Research Council. Clinical trial of the treatment of depressive illness. Brit. med. J. 1965I, 881–886
Devadatta, S., Gangadharam, P. R. J., Andrews, R. H., Fox, W., Ramakrishnan, C. V., Selkon, L. B., Velu, S.: Peripheral neuritis due to isoniazid. Bull. Wld Hlth Org. 23, 587–598 (1960)
Evans, D. A. P., Manley, K. A., McKusick, V. A.: Genetic control of isoniazid metabolism in man. Brit. med. J. 1960II, 485–491
Evans, D. A. P., White, T. A.: Human acetylation polymorphism. J. Lab. clin. Med. 63, 391–403 (1964)
Evans, D. A. P., Davison, K., Pratt, R. T. C.: The influence of acetylator phenotype on the effects of treating depression with phenelzine. Clin. Pharmacol. Ther. 6, 430–435 (1965)
Evans, D. A. P.: An improved and simplified method of detecting the acetylator phenotype. J. med. Genet. 6, 405–407 (1969)
Ganrot, P. O., Rosengren, E., Gottfries, C. G.: Effect of iproniazid on monoamines and monoamine oxidase in human brain. Experientia (Basel) 18, 260–261 (1962)
Gelber, R., Peters, L. H., Gordon, J. R., Glasko, A. J., Levy, L.: The polymorphic acetylation of dapsone in man. Clin. Pharmacol. Ther. 12, 225–238 (1971)
Goldberg, D. P., Cooper, B., Eastwood, M. R., Kedward, H. B., Shepherd, M.: A standardised psychiatric interview for use in community surveys. Brit. J. prev. soc. Med. 24, 18–23 (1970)
Greenblatt, M., Grosser, G. H., Wechsler, H.: Differential response of hospitalised depressed patients to somatic therapy. Amer. J. Psychiat. 120, 935–943 (1964)
Hare, E. H., Dominian, J., Sharpe, L.: Phenelzine and dexamphetamine in depressive illness. Brit. med. J. 1962I, 9–12
Hughes, H. B., Biehl, J. P., Jones, A., Schmidt, L. H.: Metabolism of isoniazid in man as related to the occurrence of peripheral neuritis. Amer. Rev. Tuberc. pulm. Dis. 70, 266–273 (1954)
Hutchison, J. T., Smedberg, D.: Phenelzine (Nardil) in the treatment of endogenous deoression. J. ment. Sci. 106, 704–710 (1960)
Johnstone, E. C., Marsh, W.: Acetylator status and response to phenelzine in depressed patients. Lancet 1973I, 567–570
Lascelles, R. G.: Atypical facial pain and depression. Brit. J. Psychiat. 112, 651–659 (1966)
Loomer, H. P., Saunders, L. C., Kline, N. S.: A clinical and pharmacological evaluation of iproniazid as a psychic energiser. Psychiat. Res. Rep. Amer. psychiat. Ass. 8, 129–141 (1957)
Maclean, R., Nicholson, W. J., Pare, C. M. B., Stacey, R. S.: Effect of monoamine-oxidase inhibitors on the concentrations of 5-hydroxytryptamine in the human brain. Lancet 1965II, 205–208
Peters, L. H., Gordon, G. R., Brown, P.: The relationship between the capacities of human subjects to acetylate isoniazid, sulfanilamide and sulfamethazine. Life Sci. 4, 99–107 (1965a)
Peters, L. H., Miller, K. S., Brown, P.: Studies on the metabolic basis for the genetically determined capacities for isoniazid inactivation in man. J. Pharmacol. exp. Ther. 150, 298–304 (1965b)
Rees, L., Davies, B.: A controlled trial of phenelzine (Nardil) in the treatment of severe depressive illness. J. ment. Sci. 107, 560–571 (1961)
Robinson, D. S., Lovenberg, W., Keiser, H., Sjoerdsma, A.: Effect of drugs on human blood platelet and plasma amine oxidase activity in vitro and in vivo. Biochem. Pharmacol. 17, 109–119 (1968)
Robinson, D. S., Nies, A., Ravaris, L., Lamborn, K.: The monoamine oxidase inhibitor, phenelzine in the treatment of depressive-anxiety states. Arch. gen. Psychiat. 30, 66–75 (1973)
Schildkraut, J. J.: The catecholamine hypothesis—a review of the supporting evidence. Amer. J. Psychiat. 122, 509–522 (1965)
Schroder, H.: Simplified method for determining acetylator phenotype. Brit. med. J. 1972III, 506–507
Sjoerdsma, A., Gates, J., Zaltzman, P., Udenfriend, S.: Identification and assay of urinary tryptamine. Application as an index of monoamine oxidase inhibition in man. J. Pharmacol. exp. Ther. 126, 217–222 (1959)
Smirnov, G. A., Kozulitzina, T. I.: Relation of the toxic action of phthivazid to the nature of its conversion in the body. Vop. med. Khim. 8, 401–406 (1962)
Spector, S., Shore, P., Brodie, B. B.: Biochemical and pharmacological effects of the monoamine oxidase inhibitors, iproniazid, 1-phenyl-2-hydrazinopropane (JB 516) and 1-phenyl-3-hydrazinobutane (JB 835). J. Pharmacol. exp. Ther. 128, 15–21 (1960)
Zeller, E. A., Barsky, J.: In vivo inhibition of liver and brain monoamine oxidase by 1-isonicotinyl-2-isopropyl hydrazine. Proc. Soc. exp. Biol. (N.Y.) 81, 459–461 (1952)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Johnstone, E.C. The relationship between acetylator status and inhibition of monoamine oxidase, excretion of free drug and antidepressant response in depressed patients on phenelzine. Psychopharmacologia 46, 289–294 (1976). https://doi.org/10.1007/BF00421116
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00421116