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)

The central action of the potential antidepressant drug pizotifen (Sandomigran) was studied in mice, rats and rabbits. Pizotifen in doses up to 10 mg/kg i.p. was ineffective in classic tests for antidepressant activity. It neither antagonized the effects of reserpine in rats (hypothermia, ptosis) nor potentiated the effects of amphetamine (in mice and rats), nialamide or L-dopa (in mice) on locomotor activity. However, its antidepressant activitiy was found in the 'despair test' in rats. On the other hand, pizotifen inhibited the head twitch reaction induced by L-5-hydroxytryptophan in mice (ED50 = 0.009 mg/kg, i.p.) and by 5-methoxytryptamine (+ tranylcypromine) in rats (ED50 = 0.45 mg/kg, i.p.). It also antagonized tryptamine-induced clonic convulsions of fore-paws in rats (ED50 = 0.35 mg/kg, i.p.), and in doses of 5--10 mg/kg s.c. inhibited hyperthermia produced by LSD in rabbits. Finally, pizotifen (0.1--0.3 mg/kg, i.v.) inhibited or abolished LSD- or quipazine-induced stimulation of the hind limb flexor reflex of spinal rats; the above effect was not due to noradrenolytic action of the drug. These results suggest that pizotifen strongly blocks the central postsynaptic serotonin receptors.
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PMID:The central action of pizotifen. 11 Dec 96

The effects of serotonin precursors, tryptophan (TP) and L-5-hydroxytryptophan (5-HTP), administered together with peripheral decarboxylase inhibitor -- Ro 4-4602 on the rectal body temperature of rats was studied. TP caused a significant hypothermia which was prevented by pretreatment with p-chlorophenylalanine (PCPA), the serotonin synthesis inhibitor. 5-HTP did not influence the body temperature or slightly decreased it. However, the significant hypothermizing effect of 5-HTP was observed in rats pretreated with spiroperidol, haloperidol or phenoxybenzamine. Methysergide or cyproheptadine -- compounds regarded as potent serotonin receptor blockers -- did not prevent the TP-induced hypothermia. In methysergide pretreated rats 5-HTP produced a considerable hyperthermia. Cyproheptadine did not influence the effects of 5-HTP on the body temperature. The results obtained suggest that cyproheptadine and methysergide fail to block those central serotonin receptors which produce hypothermia after their stimulation.
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PMID:The influence of serotonergic agents on the body temperature. 13 32

1 The effect of morphine (10 or 20 mg/kg s.c.), pethidine (25 or 50 mg/kg s.c.) or methadone (4 or 8 mg/kg s.c.) on the body temperature of nontreated and p-chlorophenylalanine-pretreated rats was studied at room (21+/-0.2 degrees C) or low ambient (12+/-0.2 degrees C) temperature. 2 Neither pethidine nor smaller doses of morphine and methadone altered the mean rectal temperature of rats kept at room temperature but larger doses of morphine and methadone produced significant hypothermia. 3 All narcotic analgesics at doses used in the present investigation produced significant hypothermia in rats maintained in a low ambient temperature. The hypothermia was prevented by naloxone (1 mg/kg s.c.). 4 The administration of p-chlorophenylalanine (PCPA, 320 mg/kg i.p.) 48 h before the narcotic injection prevented the fall in body temperature both at room and low ambient temperature. 5 The administration of narcotic analgesics at doses, which when administered by themselves did not alter the body temperature of rats, produced significant hyperthermia in rats pretreated with PCPA. 6 When rats pretreated with PCPA were given 5-hydroxytryptophan (75 mg/kg s.c.) 30 min before narcotic administration, the usual response to narcotics was restored. 7 It appears that pethidine and methadone as well as morphine have both hyperthermic and hypothermic actions in rats and that 5-hydroxytryptamine may be involved in the narcotic-induced hypothermia not only at room temperature but also at low ambient temperature.
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PMID:Role of 5-hydroxytryptamine in morphine-, pethidine-, and methadone-induced hypothermia in rats at low ambient and room temperature. 14 36

Effects of amitriptyline on rectal temperature of male rats were studied at the ambient temperature of 25 degrees C. Drugs were administered intraperitoneally. Amitryptyline elicited a dose related hypothermia. The hypothermia was attenuated by phenoxybenzamine 10 mg/kg, haloperidol 2 mg/kg, diphenhydramine 5 mg/kg, atropine 20 mg/kg, and cyproheptadine 5 mg/kg. Propranolol, at a dose of 5 mg/kg, had no effect on the hypothermia. Theophylline 50 mg/kg and dibutyryl cyclic AMP 20 mg/kg inhibited the hypothermia produced by anitriptyline. Pretreatment with parachloroamphetamine (PCA), 2 or 5 mg/kg daily for 3 days, strongly antagonized the hypothermia. In addition, pretreatment with parachlorophenylalanine (PCPA), 100 mg/kg daily for three days, reduced the brain 5-hydroxytryptamine (5-HT) concentration to 20% of the control level and completely blocked the hypothermia response. When brain 5-HT concentration recovered to 50% of the control level in PCPA treated rats following the administration of 10 mg/kg 5-hydroxytryptophan (5-HTP) the hypothermia induced by amitriptyline was restored. However, the administration of 5-HT, 5 mg/kg, to PCPA treated rats did not increase brain 5-HT concentration or restore the amitriptyline induced hypothermia (AIH). Results suggest that amitriptyline interacts with several transmitter substances to produce hypothermia. Since the ability of amitriptyline to produce hypothermia was correlated with brain 5-HT content, 5-HT might play an important role in the mediation of AIH.
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PMID:Mechanisms of amitriptyline induced hypothermia in the rat. 19 9

Elevating serotonin (5-HT) contents in brain with 5-hydroxytryptophan (5-HTP) reduced rectal temperature (Tre) in rabbits after peripheral decarboxylase inhibition with the aromatic-L-amino-acid decarboxylase inhibitor R04-4602 at two ambient temperatures (Ta), 2 and 22 degrees C. The hypothermia was brought about by both an increase in respiratory evaporative heat loss (Eres) and a decrease in metabolic rate (MR) in the cold. At a Ta of 22 degrees C, the hypothermia was achieved solely due to an increase in heat loss. Depleting brain contents of 5-HT with intraventricular, 5,7-dihydroxytryptamine (5,7-DHT) produced an increased Eres and ear blood flow even at Ta of 2 degrees C. Also, MR increased at all but the Ta of 32 degrees C. However, depleting the central and peripheral contents of 5-HT with p-chlorophenylalanine (pCPA) produced lower MR accompanied by lower Eres in the cold compared to the untreated control. Both groups of pCPA-treated and 5,7-DHT-treated animals maintained their Tre within normal limits. The data suggest that changes in 5-HT content in brain affects the MR of rabbits in the cold. Elevating brain content of 5-HT tends to depress the MR response to cold, while depleting brain content of 5-HT tends to enhance the MR response to cold.
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PMID:Changes in serotonin contents in brain affect metabolic heat production of rabbits in cold. 30 17

The effect of the 5-hydroxytryptamine (5-HT) precursor 5-hydroxytryptophan (5-HTP) on the thermoregulatory responses of unanesthetized rats were assessed at three different ambient temperatures (Ta) of 8, 22 and 31 degrees C. Intraperitoneal administration of either 5-HTP alone or 5-HTP plus R04-4602 (the peripheral decarboxylase inhibitor) produced dose-dependent hypothermia at both Ta's of 8 and 22 degrees C. The hypothermia was brought about solely by a decrease in metabolic heat production at 8 degrees C Ta. At 22 degrees C Ta, the hypothermia was due to both a decrease in metabolic heat production and an increase in tail and footsole skin temperature. However, at 31 degrees C Ta, there were no changes in rectal temperature in response to either 5-HTP or 5-HTP plus R04-4602 application. The data suggest that an increase in 5-HT levels in brain decreases heat production and/or increase heat loss and leads to hypothermia in rats.
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PMID:Elevating serotonin levels in brain with 5-hydroxytryptophan produces hypothermia in rats. 31 May 41

Three major metabolites (M1, M2, M3) of nomifensine (8-amino-1,2,3,4-tetrahydro-2-methyl-4-phenyl-isoquinoline) are formed by hydroxylation and methoxylation of the phenyl ring. They were compared with nomifensine 1. in various psychopharmacological tests in vivo, carried out in mice after oral or i.p. treatment and 2. in neurochemical in vitro studies, measuring inhibition of noradrenaline (NA), dopamine (DA), and serotonin (5-HT) uptake in rat brain synaptosomes. M1 (4'-hydroxy-nomifensine) was the most active metabolite, while M2 and M3 had little or no effect in pharmacological tests. M1 reversed reserpine hypothermia in doses greater than 2.5 mg/kg, antagonized tetrabenazine catalepsy (ED50 68 mg/kg) and reversed oxotremorine hypothermia (ED50 33 mg/kg). In these tests nomifensine was also active, being about 3-10 times more potent than M1. In contrast to nomifensine M1 had also serotoninergic activity, potentiating both phenelzine-induced twitching (ED50 11 mg/kg) and the anticonvulsant effect of 5-hydroxytryptophan. Moreover, M1 prolonged the hexobarbital sleeping time in doses greater than 10 mg/kg, prevented nicotine-induced convulsions (ED50 58 mg/kg) and reduced the oxotremorine tremor (ED50 59 mg/kg). The LD50 of M1 was 1100 mg/kg orally. In vitro M1 was equipotent with nomifensine in inhibiting DA uptake (IC50 1.5 x 10(-7) M) and twice as active in inhibiting NA uptake (IC50 1.1 x 10(-8) M). In contrast to nomifensine M1 was also a potent inhibitor of 5-HT uptake (IC50 3.3 x 10(-7) M). M2 and M3 were less active than M1 in all experiments.
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PMID:Pharmacological and biochemical studies with three metabolites of nomifensine. 40 62

Antidepressant properties of a new indene derivative, YM-08054-1, and its related compounds were compared with those of tricyclic antidepressants and viloxazine. The potencies of YM-08054-1 to inhibit uptake of both 14C-norepinephrine (14C-NE) and 14C-5-hydroxytryptamine (14C-5-HT) by the rat brain synaptosomes were similar to those of amitriptyline and imipramine. Other indene derivatives with an N-alkylated morpholine ring were proved to have less effect on the uptake of either 5-HT or NE than was YM-08054-1. YM-08054-1 was the most potent among all of the tested antidepressants in the inhibition of reserpine-induced facilitation of convulsions as well as in the potentiation of reserpine-induced facilitation of convulsions as well as in the potentiation of 5-hydroxytryptophan (5-HTP)-induced syndromes in mice, though the inhibitory effect of this agent on reserpine-induced hypothermia was weaker than that of either amitriptyline or desipramine, suggesting relatively selective effects of YM-08054-1 upon 5-HT rather than NE uptake in vivo. Neither viloxazine nor iprindole potentiated the responses to 5-HTP. YM-08054-1 was devoid of peripheral anticholinergic activity and exhibited weak local anesthetic effect as well as low acute toxicity when compared with amitriptyline. The results indicate that YM-08054-1 has a novel profile as an antidepressant agent which is quite different from that of either viloxazine or tricyclic compounds.
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PMID:Pharmacological and biochemical studies on a new compound, 2-(7-indeyloxymethyl)morpholine hydrochloride (YM-08054-1), and its derivatives with potential antidepressant properties. 48 6

Compound WA-335 (9,10-dihydro-10-(-1-methyl-4-piperidylidene)9-anthrol) was studied with regard to its antidepressant and central antiserotonin action in mice and rats. WA-335 depresses reserpine-induced hypothermia, particularly in mice, but does not affect ptosis induced with this neuroleptic. The compound diminishes spontaneous motility in mice and rats, including mice stimulated with amphetamine. WA-335 acts synergistically with amphetamine in which it potentiates stereotyping and enhances motility. The compound has no influence on the action of L-DOPA and does not alter hypothermia or increase motility induced with this amino acid. WA-335 does not affect the drop in body temperature or stereotype induced with apomorphine. In mice, WA-335 inhibits motility elicited with L-5-hydroxytryptophan, and in rats as well as mice prevents occurrence of head-twitches due to activation of serotonin neurons. The compound has no effect on the righting reflex abolished with fenfluramine in frogs, and given together with reserpine slightly counteracts abolition of this reflex. WA-335 raises the level of serotonin in the brains of rats, and lowers the level of 5-hydroxyindoleacetic acid. In addition, WA-335 exhibits cholinolytic activity and abolishes the symptoms elicited with oxotremorin in mice and rats.
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PMID:The action of compound WA-335 on the central nervous system. 94 51

With its chronic administration in a dose of 100 mg/kg lithium carbonate inhibited shaking of the head induced in mice with 5-hydroxytryptophan (5-HTP). This effect did not differ from the action following a single injection of lithium, when the interval between injection of lithium and of 5-HTP was one hour. With the interval lengthened to 24 hours the frequency of shaking diminished only under the effect of chronic administration. At the 5th, 10th and 21st day of a daily administration lithium failed to produce any effect on the hypothermal action of a reserpine-like agent Po 4-1284, but would reduce the protective action of imipramine in a ptosis test. A single injection of lithium made against the background of a chronic injection of water produced an opposite effect, viz. it significantly reduced the protective action of imipramine in hypothermia, but did not affect it with reference to ptosis. Hence, chronic administration of lithium leads to potentiation in its action of the serotonin-negative and central adreno-negative componets and to extenuating the peripheral adreno-negative component.
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PMID:[Effect of lithium on the central serotonin- and adrenergic processes after its chronic administration]. 108 64


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