Inhibitory effects of GABA(B) receptor agonists on swallowing in the dog
Anders Lehmann1, Marianne Bremner-Danielsen, Lena Brändén
1Integrative Pharmacology, Gastrointestinal Biology, AstraZeneca R&D Mölndal, Mölndal, Sweden. Anders.Lehmann@astrazeneca.com
Abstract:
The effects of the GABA(B) receptor agonists baclofen (1.4 and 7 micromol/kg i.v.) and CGP 44532 ([(2S)-3-amino-2-hydroxypropyl]methyl phosphinic acid], 0.2 and 0.7 micromol/kg i.v.) on transient lower esophageal sphincter relaxations and spontaneous and pharyngeally stimulated swallowing were investigated in conscious dogs. Both compounds inhibited transient lower esophageal sphincter relaxations dose-dependently, CGP 44532 being approximately fivefold more potent. In experiments designed to measure transient lower esophageal sphincter relaxations, spontaneous swallowing was suppressed by both compounds. When swallowing was evoked by intrapharyngeal water injection, both baclofen and CGP 44532 reduced the occurrence of primary peristalsis. It is concluded that centrally acting GABA(B) receptor agonists inhibit spontaneous and stimulated swallowing probably through an action in the central pattern generator for swallowing.
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