Abstract
We have determined the ability of several structurally related tricyclic antidepressant and tranquilizing drugs to inhibit both the type A form of monoamine oxidase (measured by 5-hydroxytryptamine deamination) and the type B form of the enzyme [measured by β-phenylethylamine (PEA) deamination] of rabbit brain mitochondria. These studies indicate that both forms of the enzyme are inhibited by all tricyclic antidepressant drugs tested and that the B form of the oxidase is more susceptible to inhibition than the A form. Tricyclic drugs which have a double bond between the ring moiety and the aliphatic side chain were the most effective inhibitors of the B form of monoamine oxidase. Thus amitriptyline inhibited PEA deamination to the greatest extent, followed in decreasing order of effectiveness by chlorprothixene, imipramine, and chlorpromazine. Furthermore, chlorination in position 3 and hydroxylation in position 2 of imipramine and N-demethylation of amitriptyline did not alter the ability of the parent compound to inhibit the deamination of PEA. Chlorpromazine also inhibited PEA deamination, whereas the pharmacologically inactive tricyclic drug chlorpromazine sulfoxide failed to inhibit this oxidative reaction.
ACKNOWLEDGMENTS We wish to thank the drug companies listed in Table 1 for providing samples of the compounds tested. We are grateful to Dr. R. Roth and Dr. B. S. Bunney for kindly supplying us with chlorimipramine, 7-hydroxychlorpromazine, and chlorpromazine sulfoxide, and to Dr. S. Gabay (Biochemical Research Laboratory, Veterans Administration Hospital, Brockton, Mass.) for sending us org GB 94.
- Copyright ©, 1975, by Academic Press, Inc.
MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
