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)

Tolazoline and a series of para-substituted analogues were examined in mice to determine the effects of para substitution on alpha-adrenoceptor antagonist potency and tissue disposition. alpha-Adrenoceptor antagonism was measured as abilities to attenuate the hypothermic or sedative actions of clonidine. In general, para substitution by electron-withdrawing metabolically stable groups (Cl, F) resulted in increased or unchanged brain levels of drug relative to tolazoline. The para substitution by electron-donating metabolically labile groups (CH3, OCH3) leads to reduced brain levels. Effects on alpha-adrenoceptor antagonist properties did not follow a similar pattern. Thus, increased or decreased antagonism of clonidine effects by para-chloro- or para-methyl-tolazoline, respectively, could be attributed solely to increased or decreased brain levels of drug. para-Fluorotolazoline did not antagonize clonidine but was present in brain at levels equivalent to those of tolazoline. para-Methoxytolazoline on the other hand could not be detected in any tissue but antagonised hypothermia more readily than sedation. These data indicate that the factors governing the disposition or alpha-adrenoceptor antagonist properties of tolazoline analogues are different and independent of each other.
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PMID:Effects of para-substitution on tissue levels and alpha-adrenoceptor antagonist properties of tolazoline. 287 65

1. In mice 1-10 mug histamine injected intraventricularly produces hypothermia.2. This hypothermia was not antagonized by chlorcyclizine administered subcutaneously or intraventricularly, but chlorcyclizine injected intraventricularly was effective in antagonizing the hypothermia produced by a subcutaneous injection of histamine.3. Pretreatment with atropine was without effect on the hypothermia produced by an intraventricular injection of 10 mug histamine.4. Amphetamine and tranylcypromine not only effectively reduced the intensity of, or abolished, the hypothermia but also reversed the response to an intraventricular injection of 10 mug histamine so that hyperthermia was produced. Pargyline was without effect.5. Tolazoline strongly potentiated the hypothermia produced by the intraventricular injection of 10 mug histamine, but phentolamine did not.6. It is concluded that at least part of the hypothermia produced by a subcutaneous injection of histamine arises as a result of an action on the central nervous system.7. The possible mechanisms by which histamine acting on the central nervous system produces hypothermia and the suggestion that histamine may have a physiological role in thermoregulation are discussed in the light of these findings.
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PMID:Hypothermia produced in mice by histamine acting on the central nervous system. 439 42