Serum and brain concentrations of pentazocine in relation to analgesic activity in mice

Serum and brain concentrations of pentazocine and its metabolite, the trans-alcohol, have been studied in mice and related to analgesic activity. The concentrations were determined fluorometrically after extraction and isolation of the compounds by partition chromatography as ion pairs. The acute intravenous toxicity (LD50) of the drug was also determined. The analgesic activity was found to reside in the unchanged pentazocine since, after the initial distribution phase, the drug elicits a higher degree of analgesia in animals showing higher brain concentrations of pentazocine. Furthermore, animals which did not show an analgesic response had higher serum concentrations of the trans-alcohol in comparison with animals showing analgesic activity, indicating a relation between analgesia and the degree of metabolism. However, the relation between the analgesic response and the brain concentration during the first 20 min after intravenous injection of the drug was poor.