Summary
Although the selective monoamine oxidase (MAO) B inhibitor, (-)deprenyl, has been shown to be free from the “cheese effect” in man after tyramine challenge, the reason for this is far from clear: it may well be independent of the selective inhibitory action of the drug, for during chronic administration there is some evidence to suggest that both A and B forms of the enzyme are equally inhibited. By-passing the putative MAO A gut barrier in the pig (chosen because it possesses MAO B alone in all other tissues) by intravenous tyramine administration into the deprenyl-pretreated animal failed to provoke a pressor response, despite substantial MAO inhibition. Conversely, clorgyline (MAO A inhibitor) pretreatment, which resulted in minimal MAO inhibition, produced a profound hypertensive response, resembling that observed with the non-MAO-inhibiting drug, isoniazid. The most parsimonious explanation for these findings may be that two separate but closely associated pharmacological effects are normally found with “orthodox” MAO inhibitors, enzyme inhibition proper and facilitation of noradrenaline release from its binding sites during tyramine challenge.
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Birkmayer, W., Riederer, P., Youdim, M. B. H., Linauer, W. The potentiation of the anti-akinetic effect after L-dopa treatment by an inhibitor of MAO-B, Deprenil. J. Neural Transm.36, 303–326 (1975).
Birkmayer, W., Riederer, P., Ambrozi, L. Implications of combined treatment with “Madopar” and l-Deprenil in Parkinson's Disease. A longterm study. Lanceti, 439–443 (1977).
Elsworth, J. D., Glover, V., Reynolds, G. P., Sandler, M., Lees, A. J., Phuapradit, P., Shaw, K. M., Stern, G. M., Kumar, P. Deprenyl administration in man: a selective monoamine oxidase B inhibitor without the “cheese effect”. Psychopharmacology57, 33–38 (1978).
Glover, V., Ashford, A., Sandler, M.: 1978, in preparation.
Glover, V., Sandler, M.: 1978, in preparation.
Glover, V., Sandler, M., Owen, F., Riley, G. J. Dopamine is a monoamine oxidase B substrate in man. Nature265, 80–81 (1977).
Innes, I. R., Nickerson, M. Norepinephrine, epinephrine, and the sympathomimetic amines. In: The Pharmacological Basis of Therapeutics, 5th ed., pp. 477–532. New York: Macmillan. 1975.
Johnston, J. P. Some observations upon a new inhibitor of monoamine oxidase in brain tissue. Biochem. Pharmacol.17, 1285–1297 (1968).
Knoll, J. Analysis of the pharmacological effects of selective monoamine oxidase inhibitors (Ciba Foundation Symposium 39), pp. 135–161. Amsterdam: Elsevier Excerpta Medica-North Holland. 1976.
Knoll, J. The possible mechanism of action of (-)deprenyl in Parkinson's disease. J. Neural Transm.43, 177–198 (1978).
Lader, M. H., Sakalis, G., Tansella, M. Interactions between sympathomimetic amines and a new monoamine oxidase inhibitor. Psychopharmacologia (Berl.)18, 118–123 (1970).
Lees, A. J., Shaw, K. M., Kohout, L. J., Stern, G. M., Elsworth, J. D., Sandler, M., Youdim, M. B. H. Deprenyl in Parkinson's disease. Lancetii, 791–795 (1977).
Pare, C. M. B., Sandler, M., Stern, G. M.: Presentation at 11th C.I.N.P. Congress, Vienna (1978).
Reynolds, G. P., Ceasar, P. M., Ruthven, C. R. J., Sandler, M. The effect of urinary pH and flow rate on monoamine output. Clin. Chim. Acta84, 225–231 (1978).
Reynolds, G. P., Elsworth, J. D., Blau, K., Sandler, M., Lees, A. J., Stern, G. M.: Deprenyl is metabolized to methamphetamine and amphetamine in man. (1978, submitted for publication.)
Riederer, P., Youdim, M. B. H., Rausch, W. D., Birkmayer, W., Jellinger, K., Seemann, D. On the mode of action of L-deprenyl in the human central nervous system. J. Neural Transm.43, 217–226 (1978).
Robinson, D. S., Lovenberg, W., Keiser, H., Sjoerdsma, A. Effects of drugs on human blood platelets and plasma amine oxidase activityin vitro andin vivo. Biochem. Pharmacol.17, 109–119 (1968).
Smith, C. K., Durack, D. T. Isoniazid and reaction to cheese. Ann. int. Med.88, 520–521 (1978).
Squires, R. F. Multiple forms of monoamine oxidase in intact mitochondria as characterized by selective inhibitors and thermal stability: a comparison of eight mammalian species. In: Monoamine Oxidases-New Vistas. Adv. Biochem. Psychopharmacol., Vol. 5, pp. 355–370. New York: Raven. 1972.
Stern, G. M., Lees, A. J., Sandler, M. Recent observations on the clinical pharmacology of (-)deprenyl. J. Neural Transm.43, 245–251 (1978).
Tringer, L., Haits, G., Varga, E.: The effect of L-E-250 (L-phenyl-isopropyl-methyl-propinylamine-HCl) in depressions. Proc. V. Conf. Hung. Ther. Invest. Pharmacol. (Soc. Pharmacol. Hung.), 111–114 (1968).
Varga, E., Tringer, L. Clinical trial of a new type of promptly acting psychonergetic agent (phenyl-isopropylmethyl-propinylamine-HCl, E-250). Acta Med. Acad. Sci. Hung.23, 289–295 (1967).
Waldmeier, P. C., Felner, A. E. Deprenil: loss of selectivity for inhibition of B-type MAO after repeated treatment. Biochem. Pharmac.27, 801–802 (1978).
Waldmeier, P. C., Delini-Stula, A., Maitre, L. Preferential deamination of dopamine by an A type monoamine oxidase in rat brain. Naunyn-Schmiedeberg's Arch. Pharmac.292, 9–14 (1976).
Yang, H.-Y., Neff, N. H. β-Phenylethylamine: a specific substrate for type B monoamine oxidase of brain. J. Pharmacol. Exp. Ther.187, 365–371 (1973).
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Sandler, M., Glover, V., Ashford, A. et al. Absence of “cheese effect” during deprenyl therapy: Some recent studies. J. Neural Transmission 43, 209–215 (1978). https://doi.org/10.1007/BF01246957
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DOI: https://doi.org/10.1007/BF01246957