Effects of phaclofen and the enantiomers of baclofen on cardiovascular responses to intrathecal administration of L- and D-baclofen in the rat

In a previous study it was found that i.t. administration of L-baclofen decreased arterial pressure and heart rate while D-baclofen differentially increased arterial pressure. The objective of the present study was to determine which of these effects was blocked by prior administration of the GABAB receptor antagonist, phaclofen, and whether the effect of one enantiomer of baclofen could be blocked by prior administration of the other. The decreases in systolic and diastolic arterial pressures and in heart rate produced by i.t. administration of 70 nmol of L-baclofen were unaffected by i.t. administration of 7, 70 or 700 nmol of D-baclofen 10 min prior to administration of L-baclofen, but were blocked by administration of 5 mumol of phaclofen given 3-5 min prior to L-baclofen. On the other hand, the increases in systolic and diastolic arterial pressures induced by i.t. administration of 700 nmol of D-baclofen were blocked by 70 nmol but not by 7 nmol of L-baclofen, as well as by 2.5 mumol of phaclofen; the effect of L-baclofen cannot be attributed to a desensitization of D-baclofen-sensitive receptors as two successive doses of D-baclofen given 7 min apart had quantitatively similar effects. Phaclofen alone increased systolic and diastolic arterial pressures and heart rate. The results are interpreted as indicating that D-baclofen is not an antagonist of L-baclofen in this paradigm; rather, they suggest that L-baclofen reduces the effects of D-baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)