Ventilatory effects of negative GABA(A) modulators in rhesus monkeys

Lisa R. Gerak, Laura E. Estupinan, Charles P. France

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

This study examined changes in ventilation produced by negative γ-aminobutyric acid(A) (GABA(A)) modulators in rhesus monkeys. The effects of Ro 15-4513, β-CCE and β-CCM were examined in four rhesus monkeys breathing air or 5% CO2 in air. When monkeys breathed CO2, minute volume (V(E) ) and frequency (f) increased, on average, to 158 and 140% of control (air), respectively. Ro 15-4513 did not modify ventilation in monkeys breathing either gas mixture; however, β-CCE and β-CCM increased V(E) and f in monkeys breathing air to between 123 and 141% of control and had no effect on ventilation of 5% CO2. Increased ventilation produced by the negative GABA(A) modulators appeared to be maximal, because ventilation was not further enhanced when the dose was increased three-fold. Each of the three negative GABA(A) modulators reversed the decreases in ventilation produced by diazepam, suggesting that these drugs are acting at benzodiazepine receptors; however, the increased ventilation produced by β-CCE and β-CCM might suggest that they have more negative efficacy than Ro 15-4513. These data extend previous findings by showing that some negative GABA(A) modulators (Ro 15-4513) do not alter ventilation and further indicate that changes in ventilation can be used to evaluate efficacy differences among GABA(A) modulators. Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)375-380
Number of pages6
JournalPharmacology Biochemistry and Behavior
Volume61
Issue number4
DOIs
StatePublished - Dec 1998

Keywords

  • Diazepam
  • Negative GABA(A) modulators
  • Rhesus monkey
  • Ro 15-4513
  • Ventilation
  • β-CCE
  • β-CCM

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

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