Abstract
1. The GABA-B receptor agonists baclofen and 3-aminopropylphosphinic acid (3-APPi) have antitussive activity in the cat and guinea pig. The purpose of this study was to investigate the sites of action of these GABA-B receptor agonists to inhibit the cough reflex. 2. Single intracerebroventricular (i.c.v.) cannulas were placed in the lateral ventricles of anaesthetized guinea pigs. Approximately 1 week later, the animals were exposed to aerosols of capsaicin (0.3 mM) to elicit coughing. Coughs were detected with a microphone and counted. 3. Cough was produced in anaesthetized cats by mechanical stimulation of the intrathoracic trachea and was recorded from electromyograms of respiratory muscle activity. Cannulas were placed for intravenous (i.v.) or, in separate groups of animals, intravertebral arterial (i.a.) administration of baclofen, 3-APPi, the centrally active antitussive drug codeine or the peripherally active antitussive drug BW443c. Dose-response relationships for i.v. and i.a. administration of each drug were generated to determine a ratio of i.v. ED50 to i.a. ED50, known as the effective dose ratio (EDR). The EDR will be 20 or greater for a centrally acting drug. 4. In the guinea pig, baclofen (3 mg kg-1, s.c.) and 3-APPi (10 mg kg-1, s.c.) inhibited capsaicin-induced cough by 50% and 35% respectively. The antitussive activity of baclofen was completely blocked by i.c.v. administration of the GABA-B receptor antagonist CGP 35348 (10 micrograms). Conversely, the antitussive effect of 3-APPi was unaffected by i.c.v. CGP 35348. However, systemic administration of CGP 35348 (30 mg kg-1, s.c.) completely blocked the antitussive activity of 3-APPi (10 mg kg-1, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
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- Adcock J. J. Peripheral opioid receptors and the cough reflex. Respir Med. 1991 Jan;85 (Suppl A):43–46. doi: 10.1016/s0954-6111(06)80253-2. [DOI] [PubMed] [Google Scholar]
- Adcock J. J., Schneider C., Smith T. W. Effects of codeine, morphine and a novel opioid pentapeptide BW443C, on cough, nociception and ventilation in the unanaesthetized guinea-pig. Br J Pharmacol. 1988 Jan;93(1):93–100. doi: 10.1111/j.1476-5381.1988.tb11409.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bolser D. C., Aziz S. M., DeGennaro F. C., Kreutner W., Egan R. W., Siegel M. I., Chapman R. W. Antitussive effects of GABAB agonists in the cat and guinea-pig. Br J Pharmacol. 1993 Sep;110(1):491–495. doi: 10.1111/j.1476-5381.1993.tb13837.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chapman R. W., Hey J. A., Rizzo C. A., Bolser D. C. GABAB receptors in the lung. Trends Pharmacol Sci. 1993 Jan;14(1):26–29. doi: 10.1016/0165-6147(93)90110-6. [DOI] [PubMed] [Google Scholar]
- Chou D. T., Wang S. C. Studies on the localization of central cough mechanism; site of action of antitussive drugs. J Pharmacol Exp Ther. 1975 Sep;194(3):499–505. [PubMed] [Google Scholar]
- Forsberg K., Karlsson J. A., Theodorsson E., Lundberg J. M., Persson C. G. Cough and bronchoconstriction mediated by capsaicin-sensitive sensory neurons in the guinea-pig. Pulm Pharmacol. 1988;1(1):33–39. doi: 10.1016/0952-0600(88)90008-7. [DOI] [PubMed] [Google Scholar]
- Karlsson J. A., Sant'Ambrogio G., Widdicombe J. Afferent neural pathways in cough and reflex bronchoconstriction. J Appl Physiol (1985) 1988 Sep;65(3):1007–1023. doi: 10.1152/jappl.1988.65.3.1007. [DOI] [PubMed] [Google Scholar]
- Lalley P. M. Biphasic effects of baclofen on phrenic motoneurons: possible involvement of two types of gamma-aminobutyric acid (GABA) receptors. J Pharmacol Exp Ther. 1983 Aug;226(2):616–624. [PubMed] [Google Scholar]
- McLeod R. L., Gertner S. B., Hey J. A. Modulation of cardiovascular function by central histamine H3 receptors in conscious guinea pigs. Eur J Pharmacol. 1991 Dec 10;209(1-2):141–142. doi: 10.1016/0014-2999(91)90027-n. [DOI] [PubMed] [Google Scholar]