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)

Previous experiments have demonstrated that upward shifts in a rat's thermic response to certain drugs may be observed when these drugs have been paired on several occasions with agents that induce hypothermia. A "conditional hyperactivity" hypothesis suggests that these upward shifts may simply reflect drug elicited increases in body movements which translate into higher temperatures. The present experiment explored this hypothesis. Atropine sulfate (10 mg/kg) was paired with sodium pentobarbital (40 mg/kg) on multiple occasions and several tests were conducted with both drugs. This treatment yielded a conditional hyperthermic response to atropine, but the drug was not found to elicit an increase in gross motor movements. Of greatest interest was the finding that the atropine, when injected 30 min prior to a hypnotic dose of pentobarbital (80 mg/kg), attenuated the hypothermia normally induced by this barbiturate while leaving the duration of hypnosis unaffected. This upward thermic shift cannot be accounted for by the "conditional hyperactivity" hypothesis because the animals were immobile while under pentobarbital's influence. These findings suggest that autonomic events, as yet unspecified, may underlie certain conditional temperature increases.
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PMID:Conditional shifts in thermic responses to sequentially paired drugs and the "conditional hyperactivity" hypothesis. 374 40

1. Chlorpromazine 15 mg/kg, given daily to cats for 2 weeks, produced a rise in homovanillic acid (HVA) content of the caudate nucleus, whereas the same dose of thioridazine lacked this effect. Of these two drugs, only chlorpromazine causes a high incidence of drug-induced Parkinsonism in man.2. In the mouse, chlorpromazine, thioridazine and haloperidol increased striatal concentrations of HVA and accelerated the disappearance of dopamine (DA) after inhibition of catecholamine synthesis with alpha-methyltyrosine. Low doses of the three compounds increased, whereas high doses reduced, the concentration of DA in the striatum. In their effects on the DA metabolism of the mouse, chlorpromazine and thioridazine had the same potency, but haloperidol was between 10 and 100 times more active than the other two drugs. In producing hypothermia and sedation, the three compounds were equiactive.3. Oxypertine, another drug apt to produce Parkinsonism in man, caused a severe reduction in striatal DA and hypothalamic noradrenaline (NA). Though the clinical signs produced in the mouse were indistinguishable from those seen after the same dose of chlorpromazine, the biochemical changes in the brain were thus quite different.4. Though all the drugs used caused temporary motor disabilities in animals, these bore no resemblance to human Parkinsonism, even when treatment was continued for 7 weeks or more as it was in cats and monkeys. The latter were treated with chlorpromazine 7.5 mg/kg daily, a dose chosen to avoid loss of weight and which may have been too small to produce toxic side-effects. It caused no changes in striatal DA turnover.5. Even at the high dose of 50 mg/kg, phenoxybenzamine did not increase DA turnover in mouse brain, but it sedated the mice as did the tranquillizers.6. Atropine sulphate, 25 mg/kg, reduced the HVA content of mouse striatum and partially antagonized the rise in HVA produced by phenothiazines. The effect was surmountable. Possible modes of action of atropine are discussed.7. At present we know of two types of biochemical changes which may occur in the brain of animals after treatment with drugs apt to cause Parkinsonism in man: a loss of cerebral catecholamines, as seen after reserpine or oxypertine, or an increase in turnover of DA as after phenothiazines and butyrophenones.
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PMID:Effect of drugs used in psychoses on cerebral dopamine metabolism. 498 1