Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iprindole, an active antidepressant in clinical use, has no effect on norepinephrine reuptake and does not bind to receptors of the noradrenergic system. Iprindole weakly antagonizes reserpine hypothermia and potentiates yohimbine toxicity. This effect is antagonized by propranolol but not by atenolol or metoprolol. In an acute dose, iprindole potentiates the effect of maprotiline on yohimbine toxicity. Beta 2-adrenergic agonists and antagonists specifically modify the effect of iprindole on spontaneous motility. These results indicate that iprindole has an indirect beta 2-mimetic effect.
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PMID:Is iprindole an indirect betamimetic drug? 290 49

In male Swiss mice, the hypothermia induced by apomorphine (10 mg/kg) was completely blocked by administration of haloperidol and d-butaclamol, but not by l-butaclamol, phenoxybenzamine, clozapine or propranolol. This substantiated the dopaminergic nature of the hypothermia induced by apomorphine. Desipramine, imipramine, chlorimipramine, fluoxetine and mazindol produced a dose-dependent blockade of apomorphine-induced hypothermia, their ED50S being 0.313, 0.733, 1.88, 6.04 and 0.0033 mg/kg, respectively. Iprindole failed to block the hypothermia induced by apomorphine. Because chlorimipramine and fluoxetine, which are relatively more selective and more potent blockers of the uptake of serotonin (5-HT) than is desipramine, were considerably less effective than the latter in antagonizing hypothermia induced by apomorphine, it was concluded that the property of blocking uptake of 5-HT alone does not contribute to the antagonism to apomorphine exhibited by the classical antidepressants. Quipazine, a 5-HT agonist, blocked the hypothermia induced by apomorphine, this effect developed tolerance on repeated administration. However, no cross-tolerance between quipazine and the antidepressants could be demonstrated. This finding provided further support for the non-involvement of 5-HT in the antagonism to apomorphine. No correlation existed between the potencies of these antidepressants to block the reuptake of norepinephrine (NE) in brain and their relative potencies to block the hypothermia induced by apomorphine. Moreover, selective depletion of high affinity binding sites for [3H]desipramine and [3H]-NE, achieved by treatment with DSP-4, failed to reduce the effectiveness of desipramine in blocking the hypothermia induced by apomorphine. Hence, inhibition of uptake of NE does not account for the antagonism by the antidepressants of apomorphine-induced hypothermia. A possibility was considered that certain antidepressants selectively blocked the hypothalamic DA receptors, thereby antagonizing the hypothermic effects of apomorphine, leaving the extra-hypothalamic dopaminergic responses of this DA agonist unaffected.
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PMID:Pharmacological studies on the antagonism by antidepressants of the hypothermia induced by apomorphine. 632 87

Iprindole is an active antidepressant in clinical practice but its mechanism of action has never been clearly defined. Serotoninergic regulation of noradrenergic neurons of locus coeruleus depends on 5-HT2 receptors. This regulatory action of the 5-HT system appears to facilitate the down-regulation of beta receptors. In behavioural tests involving the noradrenergic system, the role of iprindole, administered in subactive doses, was evaluated in the presence of subactive doses of fluvoxamine, a serotonin uptake inhibitor. Yohimbine is an alpha2 antagonist, inducing a dose-dependent toxicity. This test allows a rapid and selective screening of antidepressants with direct and indirect beta-agonist properties. Administration of iprindole displayed a toxicity of fluvoxamine in the presence of yohimbine. A 5-day pre-treatment of iprindole antagonized this potentiation unmasked after acute administration of iprindole. The down-regulation of beta receptors induced by a chronic treatment by iprindole could prevent the adrenergic expression of yohimbine's toxicity. But the down-regulation of 5-HT2 receptors also obtained with chronic treatment by iprindole, can explain this antagonism preventing fluvoxamine's action. Hypothermia induced by a high dose of apomorphine, depends on an activation of the noradrenergic system. During the interaction with fluvoxamine, iprindole unmasked an antagonism of this hypothermia due to apomorphine. The activity of a subactive dose of salbutamol, a direct beta-agonist, was evaluated in the presence of fluvoxamine on hypothermia induced by a high dose of apomorphine. The aim of this interaction was to define the beta-adrenergic property of iprindole more precisely.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Iprindole: a functional link between serotonin and noradrenaline systems?]. 817 13