D-Baclofen is an antagonist at baclofen receptors mediating antinociception in the spinal cord.
The antagonistic action of D-baclofen at baclofen receptors mediating antinociception in the spinal cord was examined. Drugs were administered intrathecally to rats and effects on nociceptive threshold evaluated in the tail flick test. L-Baclofen, D-baclofen and the racemate produced dose-related increases in tail flick latency, with L-baclofen being twice as potent as the racemate and approximately 100 times more potent than D-baclofen. When D-baclofen was injected 15 min prior to L-baclofen, it produced a dose-related inhibition of the effect of L-baclofen. Concomitant administration produced a more ambiguous effect. Antagonism appeared specific for baclofen receptors because analogues with full and partial agonist activity as well as an agonist dose of D-baclofen, but not morphine or noradrenaline, were inhibited by pretreatment with D-baclofen. gamma-Aminobutyric acid (GABA) did not increase tail flick latency either alone or following pretreatment with an uptake inhibitor or a GABA-transaminase inhibitor. Antinociception produced by intrathecal administration of Baclofen appears to result from activation of a receptor which is stereoselective for the L-isomer and can be blocked by D-baclofen in doses which have initial agonist activity. This receptor may not be a GABA subtype because GABA does not mimic the effect of baclofen and the rank order of potency of analogues differs from established GABAB systems.
D000480:Alkynes; D000613:Aminobutyrates / Q000494:pharmacology; D000614:Aminocaproates / Q000494:pharmacology; D000700:Analgesics; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018080:Receptors, GABA-B; D013116:Spinal Cord / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000480:Alkynes; D000613:Aminobutyrates; D000614:Aminocaproates; D000700:Analgesics; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C005959:2,4-diaminobutyric acid; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; C013785:4-amino-5-hexynoic acid; D009020:Morphine; D001418:Baclofen; D009638:Norepinephrine