Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
EFFECTS OF SOME 7-ARYLIDENE AND 7-HETEROARYLIDENE MORPHINAN-6-ONES ONTHE ANTINOCICEPTIVE ACTIVITY OF [D-PEN(2), D-PEN(5)]ENKEPHALIN AND [D-ALA(2), GLU(4)]DELTORPHIN-II AND ON MULTIPLE OPIOID RECEPTORS
Autore:
BHARGAVA HN; ZHAO GM; BIAN JT; NAN Y; UPADHYAYA SP; XU W; DUNN WJ; BAUER L;
Indirizzi:
UNIV ILLINOIS,DEPT PHARMACEUT & PHARMACODYNAM,HLTH SCI CTR,M-C 865,833 S WOOD ST CHICAGO IL 60612 UNIV ILLINOIS,DEPT MED CHEM & PHARMACOGNOSY,HLTH SCI CTR CHICAGO IL 60612
Titolo Testata:
Peptides
fascicolo: 5, volume: 18, anno: 1997,
pagine: 695 - 701
SICI:
0196-9781(1997)18:5<695:EOS7A7>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
MOUSE VAS-DEFERENS; BINDING-SITES; ANTAGONIST; BRAIN; HETEROGENEITY; NALTRINDOLE; MORPHINE; AGONISTS; SUBTYPES; MICE;
Keywords:
7-ARYLIDENE MORPHINAN-6-ONES; 7-HETEROARYLIDINE MORPHINAN-6-ONES; STRUCTURE-LIPOPHILICITY; MULTIPLE OPIOID RECEPTORS; [D-PEN(2), D-PEN(5)]ENKEPHALIN; [D-ALA(2), GLU(4)]DELTORPHIN II; ANTINOCICEPTION; GUINEA PIG ILEUM; MOUSE VAS DEFERENS; PARTITION COEFFICIENTS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
30
Recensione:
Indirizzi per estratti:
Citazione:
H.N. Bhargava et al., "EFFECTS OF SOME 7-ARYLIDENE AND 7-HETEROARYLIDENE MORPHINAN-6-ONES ONTHE ANTINOCICEPTIVE ACTIVITY OF [D-PEN(2), D-PEN(5)]ENKEPHALIN AND [D-ALA(2), GLU(4)]DELTORPHIN-II AND ON MULTIPLE OPIOID RECEPTORS", Peptides, 18(5), 1997, pp. 695-701

Abstract

The in vivo and functional effects of several 7-arylidene and 7-heteroarylidene morphinan-6-ones were determined at the mu-, delta-, and kappa-opioid receptors using the guinea pig brain membranes, guinea pig ileum (GPI), and mouse vas deferens (MVD). in vivo effects included the antagonism by these compounds given subcutaneously on the antinociceptive actions of intracerebroventricularly injected [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and [D-Ala(2), Glu(4)] deltorphin II (deltorphin II), the highly selective putative delta(1)- and delta(2)- opioid receptor agonists. Finally, the partition coefficients of these compounds were estimated (CLOGP) and determined experimentally at pH 7.4 in the 1-octanol/water system. Compared with E-7-benzylidenenaltrexone (BNTX), most compounds except for E-7 (4-chlorobenzylidene)naltrexone, were more potent at delta-opioid receptors than at the mu-opioid receptor, whereas, in comparison to the kappa-opioid receptor, the activities ofthe E-7-arylidene or E-7-heteroarylidene naltrexone derivatives at the delta-receptor were in the following order, when the 7-substituents were: 1-fluorobenzylidene > benzylidene > 3-pyridylmethylene- > 4-pyridylme thylene- > 1-methyl-2-imidazolylmethylene > 4-chlorobenzylidene. In the MVD preparation, the potencies at the delta-opioid receptor, in comparison to BNTX, were in the following order, where the 7-substituents were: benzylidene = 1-methyl-2-imidazolylmethylene- > 4-fluorobenzylidene = 3-pyridylmethylene- = 4-pyridylmethylene-. All compounds antagonized delta(1) and delta(2)-opioid receptor agonist-induced analgesia. The antagonist potencies at the delta(2)-opioid receptor were inthe following order, where the 7-substituents were: benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolylmethylene- approximate to 4-pyridylmethylene- whereasat the delta(2)-opioid receptor, the order was benzylidene- > 4-chlorobenzylidene- > 4-fluorobenzylidene- > 3-pyridylmethylene- > 1-methyl-2-imidazolylmethylene- > 4-pyridylmethylene. In general, all compoundsexhibited greater potency at the delta(2)- than delta(1)-opioid receptor. The computed partition coefficients were, as expected, greater than the apparent log P values, which were determined experimentally. Generally, the lipophilicity values in decreasing order were: 4-chlorobenzylidene- > 4-fluorobenzylidene- > benzylidene > 3-pyridylmethylene- = 4-pyridylmethylene- > 1-methyl-2-imidazolylmethylene-. In general, the benzylidene and 4-pyridylmethylene derivatives, which have medium lipophilicities, were equally effective at the delta(1)- and delta(2)- receptors; the 3-pyridylmethylene and 1-methyl-2-imidazolylmethylene derivatives had lower lipophilicities and were more selective for the delta(2)- than delta(1)- receptor; the 4-chlorobenzylidene and 4-fluorobenzylidene derivatives were more lipophilic and had intermediate activity. The plot of pED(50) values for the in vivo tests for the delta(1)- and delta(2)- receptors showed that the two receptors are not independent with respect to this series of compounds. (C) 1997 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 00:40:58