On the Reported Inhibition of Monoamine Oxidase by an Agent with Sedative Properties

Spector, Sydney; Shore, Parkhurst A.; Brodie, Bernard B.

doi:10.1126/science.132.3429.735

Cited by 13 publications

(7 citation statements)

References 4 publications

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“…These results were confirmed by Spector et al (25,26) and by Green and Erickson (27). T h e conclusions of Shore et al were based on the observation t h a t the administration of iproniazid blocked the metabolism of brain noradrenaline both in vitro and in vivo.…”

Section: Discussionsupporting

confidence: 66%

The Influence of Iproniazid and Pyrogallol on the Thermogenic Effects of Noradrenaline

Johnson

Sellers

1962

Can. J. Biochem. Physiol.

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The effects of administering a monoamine oxidase inhibitor (iproniazid) or an inhibitor of catechol-0-methyl transferase (pyrogallol) 011 the calorigenic response produced by injecting noradrenaline intravenously or subcutaneously to Wistar rats are described. The influence of isoniazid on the calorigenic response to subcutaneously administered noradrenaline was also studied. The effects of syrosingopine and tetrabenazine, with and without inhibitors, and of dl-normetanephrine, were also observed. Inhibition of monoamine oxidase increased and prolonged the calorigenic response to exogenous noradrenaline or to noradrenaline released endogenously. Isoniazid, chemically related to iproniazid but not an inhibitor of monoamine oxidase, or pyrogallol, caused little change in the calorigenic response. Thus oxidative deamination appears to be the primary reaction responsible for the termination of the calorigenic response.'Manuscript

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Section: Discussionsupporting

confidence: 66%

The Influence of Iproniazid and Pyrogallol on the Thermogenic Effects of Noradrenaline

Johnson

Sellers

1962

Can. J. Biochem. Physiol.

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“…The 2 h interval was chosen to correspond with the time of maximal change observed by Spector, Shore & Brodie (1960). For estimation of brain 5-HT, rats were stunned before decapitation and the brains rapidly removed.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of drug-induced anorexia in rats by methysergide

Barrett

McSHARRY

1975

Journal of Pharmacy and Pharmacology

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Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded. The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist.

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“…Spector et al (17) evidenced that PIH produced a rapid elevation of 5-HT content in the brain which reached a maximum within 1 to 2 hours after administration, while the noradrenaline level increased more slowly and to a lesser degree, and at the 24th hour after PIH the 5-HT level of brain was increased more than that of noradrenaline. It seemed likely that the factors producing a rise in body temperature would mainly be the 5-HT increase in brain simply because a significant increase in body temperature was observed approximately two and one-half hours after the administration of reserpine to an animal given with PIH 5 hours before the dose of reserpine.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the action of reserpine has been found to be associated with the depletion of 5-hydroxytryptamine (5-HT) or catecholamine in the brain and the direct action of the alkaloid itself would be, if any, fairly negligible (6-12). After monoamine oxidase inhibitors had been introduced to pharmacology their effects were also studied on the reserpine action by many authors (13)(14)(15)(16)(17)(18)(19)(20). Tyramine is known to have a pyrogenic action.…”

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confidence: 99%

Effect of Reserpine on Febrile Responses Induced by Pyrogenic Substances

Yasuda

1962

Japanese Journal of Pharmacology

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Although there are many reports as to the hypothermic effect of reserpine (1-5), the exact mechanism of this action appears to be undecided. Recently, the action of reserpine has been found to be associated with the depletion of 5-hydroxytryptamine (5-HT) or catecholamine in the brain and the direct action of the alkaloid itself would be, if any, fairly negligible (6-12). After monoamine oxidase inhibitors had been introduced to pharmacology their effects were also studied on the reserpine action by many authors (13)(14)(15)(16)(17)(18)(19)(20). Tyramine is known to have a pyrogenic action. Bachtold and Pletscher (21) demonstrated that rabbits pretreated with iproniazid exhibited a marked hyperthermia by the subsequently administered tyramine, phenylethylamine, 5-HT or reserpine. Horita (22) and Horita and Gogerty (23) showed that the pyrogenic activity of 5-hydroxytrypto phane, a possible precursor of 5-HT, was greatly enhanced by pretreatment with either iproniazid or beta-phenylisopropylhydrazine (PIH). In addition, Horita (22) has found that preliminary treatment of rabbits with PIH produced a marked excitation and hyperther mia with subsequent administration of reserpine. Such "reserpine reversal" was also observed between iproniazid and reserpine except in a few cases (19)(20)(21)23). Kroneberg et al. (24) have shown that the pyrogenic effect of E. coli lipopolysaccharide (LPS), purified by the method of Westphal et al. (25) is inhibited by pretreatment with reserpine and that the fever thus inhibited reappeared when iproniazid is given. Going (26) has confirmed this finding and has reported the augmentation of febrile responses of animals to bacterial pyrogens by pretreatment with iproniazid. These interesting results may indicate that biogenic amines such as 5-HT or cate cholamines could play an important role in the pyrogenic activity of bacterial pyrogens. The question remains whether the bacterial endotoxins injected intravenously in animals gain access to the brain by crossing the blood-brain barrier or it is possible that the bacterial endotoxin may not have a direct action on the thermoregulatory center, and that the active principle transferrable across the blood-brain barrier may be some of the products, derived from bacterial endotoxins. Another possibility involves a substance in the animal body produced secondarily to the effect of bacterial pyrogens. This, in sub stance, covers the two theories on pyrogenic effects of bacterial pyrogens, i.e., 'endogenous pyrogen' (27-31) and 'endogenous serum pyrogen ' (32-34).The present paper deals with a study of the possible relationship between the biogenic amine and the pyrogenic effects of several substances, bacterial as well as chemical in

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On the Reported Inhibition of Monoamine Oxidase by an Agent with Sedative Properties

Abstract: 1-Benzyl-2-methyl-5-methoxytryptamine has been reported, on the basis of indirect evidence, to inhibit monoamine oxidase. More direct experiments, however, demonstrate that the drug is devoid of the ability to block monoamine oxidase in brain in vitro or in vivo.

Cited by 13 publications

References 4 publications

The Influence of Iproniazid and Pyrogallol on the Thermogenic Effects of Noradrenaline

The Influence of Iproniazid and Pyrogallol on the Thermogenic Effects of Noradrenaline

Inhibition of drug-induced anorexia in rats by methysergide

Effect of Reserpine on Febrile Responses Induced by Pyrogenic Substances

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