3‐Aminopropylphosphinic acid—a potent, selective GABAB receptor agonist in the guinea‐pig ileum and rat anococcygeus muscle

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Abstract
3‐Aminopropylphosphinic acid, a γ‐aminobutyric acid (GABA) analogue, was tested for activity on guinea‐pig isolated ileum and rat isolated anococcygeus muscle preparations. The effects of 3‐aminopropylphosphinic acid were compared with those of GABA and baclofen. In the electrically stimulated ileum, 3‐aminopropylphosphinic acid, like GABA and baclofen, caused a concentration‐dependent inhibition of the cholinergic twitch contraction, the IC50 value being 1.84 ± 0.23 μm (n = 12). Unlike GABA, but like baclofen, 3‐aminopropylphosphinic acid did not produce an initial contraction. The inhibitory effects of 3‐aminopropylphosphinic acid and baclofen in the guinea‐pig ileum were not significantly antagonized by bicuculline (10 μm), phentolamine plus propranolol (both 1 μm), yohimbine (1 μm), naloxone (1 μm), impromidine (1 μm) or 8‐phenyltheophylline (10 μm). The inhibitory effects of 3‐aminopropylphosphinic acid, but not of baclofen, were however antagonized by phaclofen (500 μm). In addition the effects of 3‐aminopropylphosphinic acid were abolished by baclofen desensitization in the guinea‐pig ileum. 3‐Aminopropylphosphinic acid, GABA and baclofen reduced the twitch contraction evoked by electrical field stimulation in the rat anococcygeus muscle. The IC50 for 3‐aminopropylphosphinic acid inhibition of the anococcygeus contraction was 0.89 ± 0.15 μm (n = 8). It is concluded that 3‐aminopropylphosphinic acid is a potent, selective GABAB agonist, being seven times more potent than baclofen in the guinea‐pig ileum and five times more potent than baclofen in the rat anococcygues muscle preparations.