title: In vivo evidence for the efflux transport of pentazocine from the brain across the blood-brain barrier using the brain efflux index method.
abstract: The efflux transport of pentazocine (PTZ) from the brain across the blood-brain barrier (BBB) was investigated using the Brain Efflux Index method. PTZ was eliminated with the apparent elimination half-life of 13.0 min after microinjection into the parietal cortex area 2 region of the rat brain. The apparent efflux clearance of PTZ across the BBB was 137 microl/min/g brain, which was calculated from the elimination rate constant (5.35 x 10(-2) min(-1) and the distribution volume in the brain (2.56 ml/g brain). The efflux transport of PTZ was decreased in the presence of unlabeled PTZ, suggesting that PTZ is eliminated by a carrier-mediated transport system across the BBB. To characterize the efflux transport of PTZ from the brain in vivo, the effects of several compounds on the efflux transport of PTZ were investigated. P-glycoprotein (P-gp) inhibitors (verapamil and quinidine) reduced the PTZ efflux transport. In addition, the efflux transport of PTZ was inhibited by organic cations such as l-carnitine and tetraethylammonium (TEA), whereas organic anions such as p-aminohippuric acid, probenecid and taurocholate did not affect the PTZ efflux transport. The present results suggest that PTZ is transported from the brain across the BBB via l-carnitine/TEA-sensitive carrier-mediated efflux transport system(s) in addition to P-gp.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Nihon University, 7-7-1 Narasinodai, Funabashi, Chiba 274-8555, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Moriki
authors.forename: Toyofumi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furuishi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fukami
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tomono
authors.forename: Jun
authors.initials: J
authors.lastname: Watanabe
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006207:Half-Life; D007444:Inulin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics; D008297:Male; D008845:Microinjections; D010423:Pentazocine / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D011802:Quinidine / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019789:Tetraethylammonium / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D004337:Drug Carriers; D014316:Tritium; D019789:Tetraethylammonium; D007444:Inulin; D014700:Verapamil; D011802:Quinidine; D010423:Pentazocine; D002331:Carnitine