Effect of baclofen enantiomorphs on the spinal trigeminal nucleus and steric similarities of carbamazepine.
The seemingly structurally different drugs, baclofen and carbamazepine, have a similar neurophysiologic effect on the cat spinal trigeminal nucleus and a similar clinical effect in the amelioration of trigeminal neuralgia pain. In this investigation, we report on the enhancement of segmental inhibition by carbamazepine and l-baclofen; d-baclofen produced no effect on segmental inhibition. Doses of l-baclofen one fifth its equivalent racemic dosage produced a much greater enhancement of segmental inhibition. d-Baclofen, when given prior to l-baclofen, blocked the effect of l-baclofen on segmental inhibition and the unconditioned response at previously effective doses. Pretreatment with d-baclofen also blocked the effect of subsequent carbamazepine on segmental inhibition, but had no effect on the unconditioned response. Crystallographic evaluation of carbamazepine and the enantiomorphs of baclofen revealed a surprisingly good fit of baclofen isomers to moieties of the carbamazepine molecule. The results suggest that the baclofen enantiomorphs and carbamazepine have a common mechanism of action in the cat spinal trigeminal nucleus, and that d-baclofen, though inactive, is capable of interfering with the effect of l-baclofen and to a lesser extent with carbamazepine.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology*; D002415:Cats; D003461:Crystallography; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects*
D002220:Carbamazepine; D001418:Baclofen