Antinociceptive effects of two deltorphins analogs in the tail-immersion test in rats
| Autor: | Ewa Gibula-Bruzda, Jan Izdebski, Jolanta Kotlinska, Ewa Witkowska, Nga N. Chung, Peter W. Schiller |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Nociception Agonist Physiology medicine.drug_class Narcotic Antagonists Analgesic Pharmacology Biochemistry Article Cellular and Molecular Neuroscience chemistry.chemical_compound Endocrinology Drug tolerance Naltrindole Receptors Opioid delta medicine Animals Rats Wistar Pain Measurement Morphine Receptors Opioid kappa Antagonist Drug Synergism Drug Tolerance Naltrexone Rats Analgesics Opioid Opioid chemistry Deltorphin Oligopeptides medicine.drug |
| Zdroj: | Peptides. 39:103-110 |
| ISSN: | 0196-9781 |
| Popis: | The antinociceptive effects of analogs of deltorphins: cyclo(Nδ,Nδ-carbonyl-D-Orn2, Orn4)deltorphin (DEL-6) and deltorphin II N-(ureidoethyl)amide (DK-4) after intracerebroventricular (i.c.v.) administration were investigated in the tail-immersion test in rats. Morphine, the most commonly used μ-opioid receptors (MOR) agonist, was employed as a reference compound. The contribution of the MOR, δ-(DOR) and κ-opioid receptors (KOR) in antinociceptive effects of the deltorphins analogs was studies using selective antagonists of these receptors. The results indicated that DK-4 (5, 10 and 20 nmol) and DEL-6 (5, 10 and 20 nmol) were the most effective in alleviating thermal pain at the dose of 20 nmol. The antinociceptive potency of DEL-6 at the dose of 20 nmol was approximately equal but DK-4 at the dose of 20 nmol was less effective than morphine at the dose of 13 nmol. DOR antagonist – naltrindole (NTI, 5 nmol) very strongly and, to the lower extent MOR antagonist – β-funaltrexamine (β-FNA, 5 nmol), inhibited antinociceptive effect of DK-4 (20 nmol). In turn, β-FNA was more potent than NTI in inhibition of the antinociceptive effects of DEL-6. Co-administration of DEL-6 and morphine at doses of 5 nmol, which do not produce measurable antinociception, generated additive antinociceptive effect. Chronic intraperitoneal (i.p.) injection of morphine (9 days) displayed a marked analgesic tolerance to the challenge dose of morphine and a slight cross-tolerance to challenge doses of DEL-6 and DK-4, given i.c.v. These findings indicate that the new deltorphin analogs recruit DOR and MOR to attenuate the nociceptive response to acute thermal stimuli. |
| Databáze: | OpenAIRE |
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