Antinociception produced by the peptidase inhibitor, RB 101, in rats with adrenal medullary transplant into the spinal cord.
This study was undertaken to investigate the effects induced by the systemic administration of RB 101 [N-[(R,S)-2-benzyl-3[(S)(2-amino-4-methylthio)butyl dithio]-1-oxoprpyl]-L-phenylalanine benzyl ester], a mixed inhibitor of the enkephalin catabolism able to cross the blood-brain barrier, in antinociception produced by adrenal medullary tissue transplanted in the rat spinal subarachnoid space. For this purpose, the antinociceptive responses induced by intravenous (i.v.) administration of RB 101 were evaluated in the tail-flick in rats transplanted 28 and 56 days before the test. Systemic administration of RB 101 induced antinociceptive effects in sham-operated rats, as previously reported. RB 101 also enhanced significantly the antinociception produced by the autotransplant 28 and 56 days after surgery. The antinociceptive responses of RB 101 in both sham-operated and autotransplanted rats were blocked by naloxone, but were not modified by the noradrenergic antagonist, phentolamine, suggesting a selective involvement of opioid mechanisms. The present results indicate that the inhibitors of enkephalin catabolism enhance the antinociception induced by adrenal medullary transplants.
Département de Pharmacochimie Moléculaire et Structurale, U266 INSERM, URA D1500 CNRS, UFR des Sciences Pharmaceutiques et Biologiques 4, Paris, France.
A
A
Ortega-Alvaro
A J
AJ
Chover-Gonzalez
R
R
Lai-Kuen
J A
JA
Mico
J
J
Gibert-Rahola
M C
MC
Fournié-Zaluski
B P
BP
Roques
R
R
Maldonado
D000313:Adrenal Medulla / Q000637:transplantation*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D004220:Disulfides / Q000627:therapeutic use*; D007275:Injections, Intravenous; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000517:prevention & control*; D010646:Phentolamine / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord; D013346:Subarachnoid Space; D014182:Transplantation, Autologous
D000317:Adrenergic alpha-Antagonists; D004220:Disulfides; D009292:Narcotic Antagonists; D011480:Protease Inhibitors; C074024:RB 101; D009270:Naloxone; D010649:Phenylalanine; D010646:Phentolamine