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 pentazocine (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 (Jmax), 3.6 +/- 1.2 micromol/min/g brain and the apparent Michaelis constant (K1), 3.7 +/- 1.7 mM for the saturable component of PTZ into the brain, and the nonsaturable uptake rate constant (Kd), 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 H1-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.
Suzuki
Toyofumi
T
Department of Pharmaceutics, College of Pharmacy, Nihon University, Funabashi, Chiba, Japan. t-suzuki@pha.nihon-u.ac.jp
Moriki
Yoshiaki
Y
Goto
Hiroko
H
Tomono
Kazuo
K
Hanano
Manabu
M
Watanabe
Jun
J
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D017536:Carotid Artery, Common / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D010423:Pentazocine / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D010423:Pentazocine