Interactions of tricyclic antidepressant drugs with human and rat monoamine oxidase type B.
The effect of tricyclic antidepressant drugs on the deamination of phenylethylamine and benzylamine by monoamine oxidase (MAO) type B was investigated in vitro in human brain cortex, human platelet, and rat brain preparations. These drugs inhibited MAO activity as expected; however, an atypical biphasic response was observed with the tertiary amine tricyclic, clomipramine, and, to a somewhat lesser extent, with two other tertiary amine tricyclics, imipramine and amitriptyline, when benzylamine was used as the substrate in human tissue preparations. This atypical biphasic pattern was not found when we used the secondary amine antidepressant drugs, desipramine, desmethylclomipramine, or fluoxetine, or used phenylethylamine as the substrate, or used rat rather than human brain tissue. For the tricyclics exhibiting normal inhibition patterns, the same rank order of inhibition was observed with benzylamine as a substrate in all three types of tissue; however with phenylethylamine, differences in inhibition were found between rat and human tissues. These tricyclic-MAO interactional data suggest that secondary and tertiary amine tricyclics interact differently with human MAO type B, that rat and human MAO type B are not functionally identical, and also support other data that phenylethylamine and benzylamine are deaminated by different mechanisms.
Reid
A A
AA
Section on Clinical Neuropharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Hill
J L
JL
Murphy
D L
DL
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001596:Benzylamines / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology; D003641:Deamination; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000929:Antidepressive Agents, Tricyclic; D001596:Benzylamines; D010627:Phenethylamines; D008995:Monoamine Oxidase