Inhibition of rat brain monoamine oxidase by insecticides, acaricides and related compounds

Abstract

1. 1. Sixty-one insecticides, acaricides and related compounds were examined for their potency as in vitro inhibitors of the deamination of biogenic amine substrates by rat brain monoamine oxidase (MAO). Substrates examined included serotonin (5-HT), dopamine (DA), octopamine (OCP), tryptamine (TYP), and β-phenylethylamine (PEA). 2. 2. Twenty-eight compounds, including six organophosphates, four carbamates, eight formamidines, and two sulfonates, were considered active, since they gave greater than 50% inhibition of the deamination of at least one substrate when assayed at a concentration of 1 × 10 −4 M. 3. 3. Generally the active compounds were more potent MAO inhibitors when assayed with 5-HT or DA than with OCP, TYP, or PEA. 4. 4. Five of the six active organophosphates possessed a substituted coumarinyl moiety. Potosan or O, O-diethyl O-(4-methyl-7-coumarinyl) phosphorothioate was the most potent organophosphate MAO inhibitor giving pI 50 values of 5.95 and 5.75 for DA and 5-HT, respectively; inhibition of 5-HT deamination by Potasan was mixed. 5. 5. Carbaryl or 1-naphthyl methylcarbamate was the most potent carbamate with pI 50 values of 5.00 for DA and 4.80 for 5-HT. Inhibition by carbaryl of 5-HT, DA, and OCP deamination was competitive, while that of TYP was mixed. 6. 6. The formamidine chlordimeform or N′-(4-chloro- o-tolyl)- N, N-dimethyl-formamidine gave pI 50 values of 4.50 for DA and 4.25 for OCP; its N-demethyl derivative, demethylchlordimeform, was somewhat more potent giving pI 50 values of 4.80 for DA and 4.60 for OCP. Inhibition of DA and OCP deamination by chlordimeform was competitive. 7. 7. Ovex or p-chlorophenyl p-chlorobenzenesulfonate was the most potent inhibitor of 5-HT and DA deamination with pI 50 values of 6.15 and 5.90, respectively; its pI 50 value with PEA was only 2.50. Thus ovex was greater than 4000 times more potent against rat brain MAO when assayed with 5-HT (MAO-A) than with PEA (MAO-B). Inhibition by ovex was mixed with all substrates examined.