Dose-dependent potentiation or inhibition by Ro4-4602 of 5-HTP hyperthermia in rabbits

Gardey-Levassort, C; Lechat, P

doi:10.1111/j.2042-7158.1974.tb09273.x

Cited by 5 publications

(2 citation statements)

References 11 publications

(1 reference statement)

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“…We have previously demonstrated (14) that in lower doses, Ro4-4602, on the contrary, potentiates the temperature changes induced by 5-HTP, so that the inhibitory effect of Ro4-4602 on 5-HTP hyperthermia ap pears to be a function of the dose employed. The present observations show that the temperature effects of 5-HTP can be inhibited, even when the concentrations of 5-HT in the hypothalamus and brain stem are elevated.…”

Section: Inhibition By Ro4-4602 O F 5-htp-induced Hyperthermia Beformentioning

confidence: 99%

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Action of Probenecid on the Central Nervous System of the Rabbit

Gardey-Levassort¹,

Olive²,

Lechat³

1974

Pharmacology

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In rabbits pretreated with i.p. probenecid, the hyperthermia induced by 5-hydroxytryptophan (5-HTP) was markedly potentiated. There was, however, no change in the level of 5-hydroxytryptamine (5-HT) in the hypothalamus and brain stem. Consequently, there is no direct relation in this situation between hyperthermia and the cerebral levels of 5-HT. High doses of Ro4-4602 inhibited the hyperthermic effect of 5-HTP and of 5-HTP in the presence of probenecid, although the levels of 5-HT in the hypothalamus and brain stem were elevated. At the same time, a decrease in the concentration of 5-hydroxyindolacetic acid (5-HIAA) was observed in the cerebrospinal fluid (CSF). The authors suggest from their findings that Ro4-4602 may inhibit the abnormal synthesis of 5-HT induced by an excess of 5-HTP in hypothalamic thermoregulatory structures other than 5-hydroxytryptaminergic structures.

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Section: Inhibition By Ro4-4602 O F 5-htp-induced Hyperthermia Beformentioning

confidence: 99%

“…For this purpose, the decarboxylation of 5-HTP into 5-HT was blocked using Ro4-4602 (TV1 [Z),L-seryl]-Af2-[2,3,4-trihydroxybenzyl]-hydrazine), as a decarboxylase inhibitor. This substance is known to act primari ly at the periphery (2,3), but in high doses it has a central effect (4,9,11,14).…”

mentioning

confidence: 99%

Action of Probenecid on the Central Nervous System of the Rabbit

Gardey-Levassort¹,

Olive²,

Lechat³

1974

Pharmacology

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Neuroleptic influence on hyperthermia induced by 5-hydroxytryptophan and p-methoxy-amphetamine in MAOI-pretreated rabbits

Fjalland

1979

Psychopharmacology

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5-Hydroxytryptophan (5-HTP) and p-methoxyamphetamine (p-MA) induce dose-dependent, lethal hyperthermia when applied intravenously to monoamine oxidase inhibitor (MAOI) pretreated rabbits. The time course of hyperthermia and the doses required to induce hyperthermia varies between the two substances. Results with alpha-MT and PCPA suggest that 5-HTP hyperthermia depends on 5-HT formation, release of endogenous 5-HT, and the presence of catecholamines, whereas p-MA-induced hyperthermia most likely is a result of indirect 5-HT release. Some neuroleptics (piflutixol, spiroperidol and methiotepine) are extremely potent inhibitors of the induced hyperthermia, Also the 5-HT receptor blocking agent methergoline antagonizes hyperthermia induced by the two substances in rather low doses. On the other hand cis (Z)-flupenthixol is a very weak antagonist of 5-HTP but a more potent inhibitor of p-MA hyperthermia. It is concluded that both 5-HT and catecholamine (dopamine) receptor blockade is required to antagonize 5-HTP hyperthermia and that antagonism of p-MA induced hyperthermia is primarily a result of influence on the 5-HT system.

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