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Some pharmacological and biochemical properties of γ-morpholino-butyrophenone (NSD 2023), a new monoamine oxidase inhibitor

1968; Elsevier BV; Volume: 17; Issue: 3 Linguagem: Inglês

10.1016/0006-2952(68)90247-5

1873-2968

Richard F. Squires, J. Buus Lassen,

Electrochemical sensors and biosensors

Some pharmacological and biochemical properties of γ-morpholino-butyrophenone (NSD 2023) are described. NSD 2023 has a weak sedative effect of 30–60 min duration, and a more pronounced anticonvulsant effect of similar duration, when the substance is administered subcutaneously. In tests for reserpine antagonism (reversal of reserpine induced hypthermia and ptosis), and monoamine oxidase (MAO) inhibition in vivo, the substance showed a pronounced effect of at least 4 hr duration. NSD 2023 inhibits mouse brain MAO maximally within 5 min after oral administration. The time required for the reappearance of 50 per cent of inhibited MAO is dose dependent and varies from about 5–17 hr. The maximum inhibition obtainable in vivo is about 80 per cent, and the oral dose required to produce 50 per cent of maximum inhibition is about 1.4 mg/kg. In vitro, maximum inhibition is about 55 per cent, and the concentration of NSD 2023 required to produce half-maximum inhibition is about 25 gmg/ml. Pretreatment of mice with SKF 525A has no apparent effect on the subsequent inhibition of brain MAO by NSD 2023 in vivo. Pretreatment of mice with NSD 2023 protects brain MAO against inhibition by phenelzine, pargyline, tranylcypromine, and iproniazid. Similarly, pretreatment with harmaline protects against inhibition by NSD 2023. MAO inhibition by NSD 2023 is only slightly reversed by repeated washes of the mitochondria. A single oral administration of NSD 2023 (50 mg/kg) increases the serotonin content of rat brain by about 50 per cent, but has no significant effect on the concentration of noradrenaline. Pretreatment of rats with NSD 2023 antagonizes the amine depleting action of reserpine. In mice, MAO in brain and kidney is inhibited more than MAO in liver. It is suggested that the antireserpine and anticonvulsant effects of NSD 2023 are not dependent on MAO inhibition as measured using tryptamine or kynuramine as substrate. It is also suggested that the incomplete inhibition of MAO by NSD 2023 reflects the existence of two or more forms of the enzyme.