Kinetics of drug action in disease states. XXXVIII: Effect of body temperature on the convulsant activity of pentylenetetrazol in rats.

Abstract:

:The purpose of this investigation was to determine the effect of body temperature on the pharmacodynamics (convulsant activity) of pentylenetetrazol (PTZ). Rats received an iv infusion of PTZ until the onset of maximal seizures, at which time samples of cerebrospinal fluid (CSF), brain, and blood (for serum) were obtained for subsequent determination of PTZ concentrations by HPLC. The PTZ infusion caused a decrease in body temperature of approximately 4 degrees C within 20 min and onset of seizures in approximately 40 min. Compared with animals whose temperature was maintained in the normal range by heating pads, the hypothermic rats required significantly larger doses and higher serum, brain, and CSF concentrations of PTZ to produce seizures. Other rats received an injection of brewer's yeast to produce fever. Then, PTZ was infused 6, 12, or 24 h later when body temperature was elevated by an average of 1.3, 1.1, or 0.4 degrees C, respectively. Compared with control rats, whose temperature was maintained in the normal range by heating pads, moderate hyperthermia had no significant effect on the dose and concentrations of PTZ required to produce maximum seizures. Pentylenetetrazol exemplifies a drug that can produce hypothermia which, in turn, reduces the sensitivity of rats to its pharmacologic action. Unlike the central nervous system (CNS) depressants phenobarbital and ethanol, whose pharmacologic activity in rats is enhanced at elevated body temperature, the activity of the CNS stimulant PTZ is apparently not altered by fever.

journal_name

J Pharm Sci

authors

Walker JS,Levy G

doi

10.1002/jps.2600801005

subject

Has Abstract

pub_date

1991-10-01 00:00:00

pages

928-30

issue

10

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)48672-1

journal_volume

80

pub_type

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