ANALGESIC ACTIVITY AND CENTRAL NERVOUS SYSTEM DISTRIBUTION OF THE OPTICAL ISOMERS OF PENTAZOCINE IN THE RAT

¹ Department of Pharmacology, University of California Medical Center, San Francisco, California

Onset, intensity and duration of analgesia produced by the dl-, d-and l-isomers of pentazocine were measured by the blockade of the pain response elicited by i.a. bradykinin administration. Most of the analgetic activity of pentazocine was found to reside in the l-isomer; the d-isomer was weakly analgetic at 15 mg/kg. Peak analgesia appeared to correlate reasonably well with brain and plasma levels of pentazocine, estimated by a spectrophotofluorometric procedure with a sensitivity 0.1 µg of drug per g of brain and 0.04 µg/ml of plasma. After a 15 mg/kg dose s.c., central nervous system and plasma levels of all three pentazocine isomers reached maximal values within 30 minutes. Levels of the d-isomer in eight brain regions (cortex, cerebellum, medulla-pons, midbrain, hypothalamus, hippocampus, striatum and cord) tended to be slightly higher and to fall more rapidly than those of the l-and the dl-isomers. Early levels of all three isomers were found to be highest in the cortex or hypothalamus and lowest in the cord but the differences between the two areas were generally less than 20%. Differences in the regional central nervous system distribution of the optical isomers of pentazocine failed to account for their differences in pharmacologic activity.