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)

Small doses of apomorphine (0.03-0.25 mg/kg i.p.) caused a dose-dependent suppression of the ethanol-induced (2.36 g/kg, 15% v/v, i.p.) locomotor stimulation in mice and higher doses (0.5--2 mg/kg i.p.) caused a delayed suppression. The delay increased with increased doses. Very small doses of clonidine (0.025 or 0.05 mg/kg i.p.), which per se did not or only slightly affect the activity of control mice, also markedly suppressed the ethanol-induced motor stimulation. Ethanol alone (2.36 g/kg i.p.) did not significantly affect the amount of Dopa accumulating in various mouse brain regions (limbic system, corpus striatum, hemispheres and brain stem) during 30 min following administration of 3-hydroxybenzylhydrazine (NSD 1015), an inhibitor of aromatic amino-acid decarboxylase. Both the hypothermia and the locomotor stimulation by ethanol were antagonized by NSD 1015. The reduction in Dopa accumulation induced by a small dose of apomorphine (0.25 mg/kg i.p.) in the dopamine-rich regions in the mouse brain was slightly enhanced by ethanol, whereas the clonidine-induced decrease in Dopa accumulation was, if anything, reduced. In conclusion, ethanol's behavioural stimulant action in mice can be largely suppressed by apomorphine or clonidine, drugs which in the small doses used probably inhibit central catecholamine (CA) neurons.
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PMID:Antagonism of ethanol's central stimulation in mice by small doses of catecholamine-receptor agonists. 40 47

Role of brain monoamines in the hyprothermic activity of cannabis resin (CI) in albino rats was studied using agents which influence monoamine synthesis, storage, release, reuptake, metabolism and receptor activity and monoaminergic neuronal activity. Delta-9-tetrahydrocannabinol content of resin was estimated to be 17%. Reserpine was used for comparison. CI was given orally in the dose of 50 mg/kg. Nialamide (NM) and alpha-methyl-metatyrosine (MMT) caused slight hyperthermia. p-Chlorophenylalanine (PCPA), alpha-methol-p-tyrosine (MPT), 5,6-dihydroxytryptamine (DHT, icv) and 6-hydroxydopamine (6-HD, icv) had no effect on body temperature. alpha-Methyl-dopa (m-Dopa), diethyldithiocarbamate (DDC), DDC with l-Dopa, gammabutyrolactone (GBL), phentolamine (PHENT), phenoxybenzamine (PBZ), propranolol (PROP) and imipramine (IMP) produced hypothermia. Hyprothermic activity of CI was potentiated by NM and PCPA, unaffected by DHT and m-Dopa, blocked by MMT, MPT, 6-HD, GBL, PHENT, PROP and chlorpromazine (CPZ), inhibited by DDC, DDC and l-Dopa and PBZ. CI induced hyperthermia in tolerant rats could be reversed to hypothermia by IMP. Reserpine hypothermia was blocked by NM, MPT, 6-HD and CPZ. There was a partial cross tolerance between cannabis and reserpine. Studies indicate that the hypothermic activity of CI similar to that of reserpine is mediated through central catecholamines and not 5-HT, and that noradrenaline is involved and not dopamine. However, the mechanism of action of cannabis and reserpine on noradrenergic neurone seems to be different.
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PMID:Role of catecholamines in the hypothermic activity of cannabis in albino rats. 82 62

Relationships between structure and duration of neurotensin's central action were examined. Included in the study were analogs containing amino acid substitutions at purported enzymatic cleavage sites of neurotensin: the arg8-arg9, the Pro10-Tyr11, and the Tyr11-Ile12 peptide bonds. Peptides were administered in rats via the cerebro-ventricular route and the ensuing hypothermia was monitored repeatedly until the effect dissipated. Results indicate that substitutions of the Tyr11 residue of the neurotensin molecule with either Dopa, Trp, D-Trp, or D-Tyr yielded analogs displaying markedly increased durations of action. Substitutions at other sites did not alter the time course of neurotensin's hypothermic effect. The longest acting analog was [Dopa11]-NT. At a dose of 7.5 micrograms the hypothermia induced by this analog persisted for 660 min while the effect of a same dose of neurotensin endured for only 90 min after injection. No clear correlation was found between the relative potency of analogs and their duration of action. Taken together, the results confirm the predominant role of Tyr11 in the inactivation of neurotensin by the brain, but do not support the hypothesis that relative potencies of structural analogs are solely dependent on differing susceptibilities to enzymatic degradation.
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PMID:Relationships between structure and duration of neurotensin's central action: emergence of long acting analogs. 651 48

Racemic 2-(di-n-propylamino)tetralin ((R,S)-DPAT), which lacks phenolic or other aromatic substituents, induces both dopaminergic (sniffing, licking and gnawing) and serotoninergic (forepaw treading and flat body posture) behavioural responses. The present study shows that s.c. administration of (R)-DPAT induces typical 5-HT1A receptor agonist behaviours. These effects are blocked by the 5-HT1A receptor antagonist (S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin ((S)-UH-301). Administration of (S)-DPAT induces dopaminergic behaviours, which are fully antagonised by raclopride, a dopamine D2 receptor antagonist. Both enantiomers induce hypothermia, (R)-DPAT being antagonised by (S)-UH-301, whereas (S)-DPAT is antagonised by raclopride. The accumulation of 5-hydroxytryptophan and DOPA (3,4-dihydroxyphenylalanine) after decarboxylase inhibition that reflects presynaptic actions on 5-HT (5-hydroxytryptamine, serotonin) and dopamine neurons, respectively, are inhibited by both enantiomers of DPAT. (R)-DPAT is more potent than (S)-DPAT as an inhibitor of 5-hydroxytryptophan accumulation whereas (S)-DPAT is more potent than (R)-DPAT as an inhibitor of DOPA accumulation. Thus, in functional tests of postsynaptic actions (R)-DPAT behaves as a 5-HT1A receptor agonist and (S)-DPAT as a dopamine D2 receptor agonist. Presynaptically, (R)-DPAT shows selectivity for 5-HT1A receptors and (S)-DPAT for dopamine D2 receptors. Receptor binding studies, utilizing [3H]8-hydroxy-2-(di-n-propylamino)tetralin and [3H]quinpirole as radioligands for 5-HT1A and dopamine D2 receptors, respectively, showed (R)-DPAT to have a 3-fold higher affinity than (S)-DPAT for 5-HT1A receptors, whereas (S)-DPAT had a 6-fold higher affinity than (R)-DPAT for dopamine D2 receptors. Thus, the results from receptor binding studies support the conclusion that (R)- and (S)-DPAT are agonists showing selectivity for 5-HT1A and dopamine D2 receptors, respectively. Taken together, these findings may explain previous controversies with regard to the pharmacology of racemic DPAT and re-emphasise the necessity to study pure enantiomers of chiral compounds.
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PMID:Differential serotoninergic and dopaminergic activities of the (R)- and the (S)-enantiomers of 2-(di-n-propylamino)tetralin. 881 61