Baclofen activates two distinct receptors in the rat spinal cord and guinea pig ileum.

Following intrathecal injection, pretreatment with both D-baclofen and 5-aminovaleric acid (5-AV) inhibited the antinociceptive effect of L-baclofen, but homotaurine (3-aminopropane sulphonic acid, APS) was inactive as an antagonist (rank order D-baclofen greater than 5-AV greater than APS = 0). In an established GABAB system, the electrically stimulated guinea pig longitudinal muscle myenteric plexus preparation, APS and 5-AV but not D-baclofen reduced the inhibitory effect of L-baclofen (APS = 5-AV greater than D-baclofen = 0). Receptors with which baclofen interacts in the spinal cord to produce antinociception differ from GABAB receptors with respect to the rank order of potency of antagonists as well as close structural analogs, and these criteria could be used for characterization of such receptors.