M. Urbaneja, C. O. Knowles
1979
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0
Influential Citations
7
Citations
Quality indicators
Journal
General pharmacology
Abstract
1. Forty-two formanilides were examined for their potency as in vitro inhibitors of rat brain monoamine oxidase (MAO). Structure-activity relationship data obtained with tryptamine as substrate indicated that for maximum MAO inhibitory activity formanilides should be substituted in ring positions 2 and 5, 2 and 4, or 2, 4, and 5. 2. The most potent formanilides tested were substituted with halogen in ring positions 2 and 5 and 2, 4, and 5. 3. Other strong di-substituted formanilide MAO inhibitors contained halogen in ring positions 2 and 4 or methyl in ring position 2 and chlorine in ring position 4 or 5. 4. The other strong tri-substituted formanilide MAO inhibitor contained methoxy at ring positions 2 and 4 and chlorine in ring position 5. 5. Structure-activity relationship data with dopamine and serotonin as substrates generally were similar qualitatively to those with tryptamine. 6. However, with β-phenylethylamine as substrate, maximum inhibitory potency of formanilides was associated with chlorine in ring position 3 and chlorine or methyl in ring position 2 or 4. 7. Generally serotonin was the most sensitive substrate to inhibition by formanilides followed in sequences by dopamine, tryptamine and β-phenylethylamine. 8. Thus, formanilides generally were more potent inhibitors of MAO-A (serotonin oxidation) than of MAO-B (β-phenylethylamine oxidation), and the selectivity differential was especially marked in some cases. For example, 5-chloro-2,4-dimethoxyformanilide was greater than 7079 times more potent against rat brain MAO when assayed with serotonin (pI50 5.85) than with β-phenylethylamine (pI50 < 2.00); four other formanilides yielded selectivity differentials ranging from 100- to 631-fold.