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 language | English (US) |
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Pages (from-to) | 375-380 |
Number of pages | 6 |
Journal | Pharmacology Biochemistry and Behavior |
Volume | 61 |
Issue number | 4 |
DOIs | |
State | Published - Dec 1998 |
Keywords
- Diazepam
- Negative GABA(A) modulators
- Rhesus monkey
- Ro 15-4513
- Ventilation
- β-CCE
- β-CCM
ASJC Scopus subject areas
- Biological Psychiatry
- Biochemistry
- Behavioral Neuroscience
- Clinical Biochemistry
- Toxicology
- Pharmacology