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Titolo:
Antinociceptive activity of [beta-methyl-2 ',6 '-dimethyltyrosine(1)]-substituted cyclic [D-Pen(2),D-Pen(5)]enkephalin and [D-Ala(2),Asp(4)]deltorphin analogs
Autore:
Bilsky, EJ; Qian, XH; Hruby, VJ; Porreca, F;
Indirizzi:
Univ No Colorado, Dept Biol Sci, Greeley, CO 80639 USA Univ No Colorado Greeley CO USA 80639 ept Biol Sci, Greeley, CO 80639 USA Univ Arizona, Dept Pharmacol, Tucson, AZ USA Univ Arizona Tucson AZ USAUniv Arizona, Dept Pharmacol, Tucson, AZ USA Univ Arizona, Dept Chem, Tucson, AZ 85721 USA Univ Arizona Tucson AZ USA 85721 Arizona, Dept Chem, Tucson, AZ 85721 USA
Titolo Testata:
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
fascicolo: 1, volume: 293, anno: 2000,
pagine: 151 - 158
SICI:
0022-3565(200004)293:1<151:AAO[''>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
OPIOID DELTA-ANTINOCICEPTION; TOPOGRAPHICAL REQUIREMENTS; DIFFERENTIAL ANTAGONISM; RECEPTOR MULTIPLICITY; ENKEPHALIN ANALOG; MOUSE; NALTRINDOLE; DELTORPHIN; MEDIATION; SUBTYPES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
18
Recensione:
Indirizzi per estratti:
Indirizzo: Bilsky, EJ Univ No Colorado, Dept Biol Sci, Greeley, CO 80639 USA Univ No Colorado Greeley CO USA 80639 i, Greeley, CO 80639 USA
Citazione:
E.J. Bilsky et al., "Antinociceptive activity of [beta-methyl-2 ',6 '-dimethyltyrosine(1)]-substituted cyclic [D-Pen(2),D-Pen(5)]enkephalin and [D-Ala(2),Asp(4)]deltorphin analogs", J PHARM EXP, 293(1), 2000, pp. 151-158

Abstract

Research in our laboratories involves the development of selective opioid agonists and antagonists as: 1) pharmacological tools to elucidate the mechanisms of opioid antinociception, and 2) potential analgesics that possess therapeutic advantages over currently available drugs. We hypothesized thatthe selectivity of peptide agonists toward the opioid receptor types and subtypes is topographically dependent. The current results assess the antinociceptive activity and opioid receptor selectivity of a series of beta-methyl-2',6'-dimethyltyrosine (TMT)-substituted cyclic [D-Pen(2),D-Pen(5)]enkephalin (DPDPE) and [D-Ala(2),Asp(4)]deltorphin (DELT I) analogs. Compounds were injected via the intracerebroventricular route into male ICR mice, and antinociception was assessed using the 55 degrees C warm water tail-flick test. Antinociceptive A(50) values ranged from 0.35 to 17 nmol for the DELT I analogs and from 7.05 to >100 nmol for the DPDPE analogs. To test for receptor selectivity, mice were treated with selective mu- and delta-opioid antagonists. In general, mu [beta-funaltrexamine (beta-FNA)]- and delta(1) ([D-Ala(2),Leu(5),Cys(6)] enkephalin)-antagonists blocked the antinociceptiveactions of [TMT1]DPDPE analogs, whereas the antinociceptive actions of [TMT]DELT I analogs were more sensitive to antagonism by the delta(2)-selective antagonist [Cys(4)]deltorphin and the mu-antagonist beta-FNA. The antinociceptive actions of the [(2R,3S)-TMT1]DELT I analog was suppressed by both [D-Ala(2),Leu(5), Cys(6)]enkephalin and beta-FNA. These results are in contrast to those found with the parent molecules DPDPE (primarily a delta(1) agonist) and DELT I (a mixed delta(1)/delta(2) agonist). These results demonstrate that topographical modification in position 1 of the DPDPE and DELT I peptides affects antinociceptive potency and opioid receptor selectivity.

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Documento generato il 03/04/20 alle ore 03:34:27