Antitussive effects of GABAB agonists in the cat and guinea-pig
Article first published online: 19 JUL 2012
1993 British Pharmacological Society
British Journal of Pharmacology
Volume 110, Issue 1, pages 491–495, September 1993
How to Cite
Bolser, D. C., Aziz, S. M., DeGennaro, F. C., Kreutner, W., Egan, R. W., Siegel, M. I. and Chapman, R. W. (1993), Antitussive effects of GABAB agonists in the cat and guinea-pig. British Journal of Pharmacology, 110: 491–495. doi: 10.1111/j.1476-5381.1993.tb13837.x
- Issue published online: 19 JUL 2012
- Article first published online: 19 JUL 2012
- Received January 25, 1993; Revised May 4, 1993; Accepted May 17, 1993
- GABAB receptors;
- 3-aminopropyl-phosphinic acid
- 1GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom of pulmonary disease, but the effects of GABAB agonists on this airway reflex are unknown. Experiments were conducted to determine the antitussive effect of GABAB receptor agonists in comparison to the known antitussive agents, codeine and dextromethorphan.
- 2Unanaesthetized guinea-pigs were exposed to aerosols of 0.3 mm capsaicin to elicit coughing, which was detected with a microphone and counted. Cough also was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity.
- 3In guinea-pigs, the GABAB agonists baclofen and 3-aminopropyl-phosphinic acid (3-APPi) produced dose-dependent inhibition of capsaicin-induced cough when administered by subcutaneous or inhaled routes. The potencies of baclofen and 3-APPi compared favourably with codeine and dextromethorphan.
- 4The GABAB antagonist, CGP 35348 (0.3– 30 mg kg−1, s.c.) inhibited the antitussive effect of baclofen (3.0 mg kg−1, s.c). However, CGP 35348 (10 mg kg−1, s.c.) had no effect on the antitussive activity of codeine (30 mg kg−1, s.c). The antitussive effect of baclofen was not influenced by the GABAA antagonist, bicuculline (3 mg kg−1, s.c.) or naloxone (0.3 mg kg−1, s.c).
- 5In the cat, baclofen (0.3–3.0 mg kg−1, i.v.) decreased mechanically-induced cough in a dose-dependent manner. In this model, baclofen (ED50 = 0.63 mg kg−1) was less potent than either codeine or dextromethorphan. The antitussive effect of baclofen in the cat was antagonized by the GABAB antagonists, CGP 35348 (10 mg kg−1, i.v.) and 3-aminopropylphosphonic acid (3 mg kg−1, i.v.).
- 6We show that baclofen and 3-APPi have antitussive effects in the guinea-pig and cat and these effects are mediated by GABAB receptors.