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Titolo:
SELECTIVE ANTAGONISM OF OPIOID ANALGESIA BY A SIGMA-SYSTEM
Autore:
CHIEN CC; PASTERNAK GW;
Indirizzi:
MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,GEORGE COTZIAS LAB NEUROONCOL,1275 YORK AVE NEW YORK NY 10021 MEM SLOAN KETTERING CANC CTR,DEPT NEUROL,GEORGE COTZIAS LAB NEUROONCOL NEW YORK NY 10021 CORNELL UNIV,COLL MED,DEPT NEUROL & NEUROSCI NEW YORK NY 00000 CORNELL UNIV,COLL MED,DEPT PHARMACOL NEW YORK NY 00000
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 271, anno: 1994,
pagine: 1583 - 1590
SICI:
0022-3565(1994)271:3<1583:SAOOAB>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
NALORPHINE-LIKE DRUGS; CHRONIC SPINAL DOG; GUINEA-PIG BRAIN; BETA-FUNALTREXAMINE; OPIATE RECEPTORS; BINDING-SITES; RAT-BRAIN; NALOXONE BENZOYLHYDRAZONE; N-ALLYLNORMETAZOCINE; RELATIVE INVOLVEMENT;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
65
Recensione:
Indirizzi per estratti:
Citazione:
C.C. Chien e G.W. Pasternak, "SELECTIVE ANTAGONISM OF OPIOID ANALGESIA BY A SIGMA-SYSTEM", The Journal of pharmacology and experimental therapeutics, 271(3), 1994, pp. 1583-1590

Abstract

(+)Pentazocine antagonizes morphine analgesia as potently as its (-) isomer, ruling out an opioid receptor mechanism of action and suggesting, which suggests a role for sigma(1) receptors. Systemic (+) pentazocine also reverses supraspinal or spinal morphine analgesia. 1,3-Di(2-tolyl)guanidine, a sigma ligand with no appreciable opioid receptor affinity, antagonizes morphine analgesia. The actions of both (+)pentazocine and 1,3di(2-tolyl)guanidine are reversed by haloperidol, which has high affinity for both sigma and D-2 receptors, but not by the D-2- selective antagonist (-)sulpiride, which lacks activity at sigma sites. The antiopioid sigma system is tonically active. Haloperidol, but not (-)sulpiride, decreases morphine ED(50) almost 2-fold. The antiopioid system modulates only mu analgesia. Unlike analgesia, (+)pentazocinedoes not influence morphine's inhibition of gastrointestinal transit or lethality. (+)Pentazocine also antagonizes kappa(1), kappa(3) and delta analgesia through sigma mechanisms in a haloperidol-sensitive manner. (-)Sulpiride is inactive. Alone, haloperidol enhances kappa(1), kappa(3) and delta analgesia more dramatically than morphine, which indicates that the sigma system is active against all opioid analgesic systems. Sigma systems are responsible for some strain differences in kappa receptor sensitivity. Unlike CD-1 mice, BALB-C mice are relativelyinsensitive toward the kappa(1) agent U50,488H and the kappa(3) analgesic naloxone benzoylhydrazone. Blockade of the sigma system with haloperidol eliminates these strain differences. In conclusion, sigma(1) systems functionally antagonize opioid analgesia without affecting morphine's effects on gastrointestinal transit or lethality. The antiopioid sigma system is tonically active and is more active against kappa analgesia than mu. The level of this tonic activity plays a significant role in strain differences in analgesic sensitivity toward opioid analgesia.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 10:21:36