Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.

The influx transport mechanism of pentazoeine (PTZ) at the blood-brain barrier (BBB) was investigated in rats using the carotid injection technique. The uptake kinetics of PTZ into the rat brain exhibited saturability, which occurred by both nonsaturable and carrier-mediated transport processes. The in vivo kinetic parameters were estimated as follows: the maximal uptake rate (J(max)), 3.6+/-1.2 mumol/min/g brain and the apparent Michaelis constant (K-t), 3.7+/-1.7 mm for the saturable component of PTZ into the brain, and the nonsaturable uptake rate constant (K-d), 0.06+/-0.04 ml/min/g brain. The uptake of PTZ by the brain was strongly inhibited by lidocaine, imipramine and propranolol, and also by H-1-antagonists such as mepyramine, diphenhydramine. In addition, narcotic-antagonist analgesic (buprenorphine, butorphanol or eptazocine) and an opioid antagonist (naloxone) significantly inhibited PTZ transport. These results suggest that PTZ permeates into the brain via a carrier-mediated transport system, which may widely recognize the cationic drugs.