Chlorpromazine-induced hypothermia and increased plasma creatine phosphokinase activity

Herbert Meltzer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The rate of efflux of creatine phosphokinase (CPK) from rat extensor digitorum longus muscle in vitro was significantly less at 22° than at 30°. Chlorpromazine (Cpz) at 10-3 M and 10-4 M, but not at 10-5 M increased the efflux of CPK in vitro. In vivo, Cpz produced levels of CPK in plasma which were significantly correlated with the hypothermia that developed after the drug was administered (R = -0.958, P < 0.001). When the hypothermia subsequent to Cpz administration was blocked by keeping rats at 31° or by administering the drug to cold acclimated rats, no increase in plasma CPK levels developed. Cpz, 25 mg/kg, produced a greater fall in body temperature and a greater increase in plasma CPK activity in rats kept at 2° than in rats kept at 22°. Cpz, given intramuscularly (i.m.) or intraperitoneally (i.p.) to rats kept at 22° produced equivalent increases in plasma CPK activity although the hypothermia following i.m. administration was slightly greater. Ganglionic blockade did not inhibit the increase in plasma CPK levels. Adrenalectomized rats did not differ from intact rats in the extent of increase in plasma CPK levels for a given degree of hypothermia. It is suggested that the increased plasma levels of CPK in vivo following Cpz in rats is due to the hypothermia produced by this drug rather than a direct toxic effect. In man, where IM Cpz does not produce hypothermia, the increased levels of CPK in plasma are probably due to the toxic effects of the drug, or its vehicle, on muscle.

Original languageEnglish (US)
Pages (from-to)1739-1748
Number of pages10
JournalBiochemical Pharmacology
Volume20
Issue number8
DOIs
StatePublished - Aug 1971

Funding

* Supported by grants from the State of Illinois No. 17-340, the United States Public Health Service No. 16127-01. the Scottish Rite Foundation and the Otho S.A. Snrague Foundation. i Recipient of a Research Career Development Award K02 M-H-47 808.

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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