Homotaurine: a GABA_B antagonist in guinea‐pig ileum

The inhibitory effects of GABA and (−)‐baclofen were prevented in the presence of homotaurine 2 × 10⁻⁴ and 10⁻³ M.

The log dose‐effect curves of GABA and (−)‐baclofen were shifted in a parallel manner compatible with competitive antagonism. The pA₂ of homotaurine with GABA (4.22 ± 0.05) and (−)‐baclofen (4.26 ± 0.1) were the same.

Homotaurine did not antagonize the inhibitory effects of morphine (ED₅₀ 4 × 10⁻⁷ M), noradrenaline (ED₅₀ 10⁻⁶ M) or ATP (ED₅₀ 1.5 × 10⁻⁵ M).

The inferior homologue of homotaurine, taurine 10⁻³ M, did not modify the inhibitory effects of GABA and (−)‐baclofen.

Picrotoxin 5 × 10⁻⁵ M antagonized GABA_A receptor‐mediated contraction but did not affect GABA_B receptor‐mediated inhibition. At the same concentration the drug did not influence the antagonistic action of homotaurine, thus showing no GABA_A receptor‐mediated interference.

It may be concluded that homotaurine is a competitive antagonist of GABA_B mediated effects in the guinea‐pig ileum.