A comparative analysis of the infarct-limiting activity of δ- and κ-opioid receptors (OR) agonists was carried out on a model of coronary occlusion (45 min) and reperfusion (120 min) in male Wistar rats. We used selective δ₂-OR agonist deltorphin II (0.12 mg/kg), δ-OR agonists BW373U86 and p-Cl-Phe DPDPE (0.1 and 1 mg/kg), selective agonists of δ₁-OR DPDPE (0.1 and 0.969 mg/kg), κ₁-OR U-50,488 (0.1 and 1 mg/kg), κ₂-OR GR-89696 (0.1 mg/kg), and κ-OR ICI-199,441 (0.1 mg/kg). All drugs were administered intravenously 5 min before reperfusion. Deltorphin II, BW373U86 (1 mg/kg), p-Cl-Phe DPDPE (1 mg/kg), U-50,488 (1 mg/kg), and ICI-199,441 had a cardioprotective effect. The most promising compounds for drug development are ICI-199,441 and deltorphin II.

2021-03-01·Bulletin of Experimental Biology and Medicine4区 · 医学

Comparative Analysis of Infarct Size Limiting Activity of κ-Opioid Receptor Agonists in In Vivo Reperfused Heart

4区 · 医学

Article

作者: Tsibulnikov, S Yu ; Mukhomedzyanov, A V ; Maslov, L N

A 45-min coronary artery occlusion followed by a 120-min reperfusion was performed in rats anesthetized with α-chloralose. The selective κ₁-opioid receptor (OR) agonist U-50,488 was administered intravenously in doses of 0.1 or 1 mg/kg. The selective κ₂-OR agonist GR-89696 was injected in a dose of 0.1 mg/kg. The selective κ₁-OR agonists ICI-199,441 and ICI-204,448 were employed in the doses of 0.1 and 4 mg/kg, respectively. These drugs were injected 5 min prior to reperfusion. U-50,488 exerted the cardioprotective effect in a dose of 1 mg/kg, but it produced no effect on infarct size in a dose of 0.1 mg/kg. ICI-199,441 reduced the reperfusion injury to the heart. The infarct size limiting effects of U-50,488 and ICI-199,441 were prevented by preliminary injection of naltrexone or nor-binaltorphimine. It is concluded that infarct size limiting effects of U-50,488 and ICI-199,441 were mediated via activation of κ₁-OR.

2017-01-01·Acta Dermato Venereologica3区 · 医学

Involvement of µ-opioid Receptors and κ-opioid Receptors in Itch-related Scratching Behaviour of Imiquimod-induced Psoriasis-like Dermatitis in Mice

3区 · 医学

ArticleOA

作者: Matsuda, Hironori ; Takamori, Kenji ; Kamata, Yayoi ; Sakaguchi, Azumi ; Kosaka, Ryohei ; Ogawa, Hideoki ; Tominaga, Mitsutoshi ; Takahashi, Nobuaki ; Umehara, Yoshie

The pathogenesis of psoriatic itch is poorly understood. The aim of this study was to investigate the involvement of opioid receptors in scratching behaviour of imiquimod-induced psoriasis-like dermatitis model mice. Topical application of 5% imiquimod cream to the rostral back skin of mice induced antihistamine-resistant scratching behaviour. The expression of µ-opioid receptor (MOR) protein increased in the epidermis, dorsal root ganglia (DRG) and spinal cord of imiquimod-treated mice. In contrast, the expression of κ-opioid receptor (KOR) protein decreased in the DRG and spinal cord of imiquimod-treated mice, and was undetectable in the epidermis of both groups. Topical or intraperitoneal administration of the MOR antagonist naloxone and oral administration of the centrally acting KOR agonist ICI-199,441 inhibited scratching behaviour, whereas oral administration of the peri-pherally-selective KOR agonist asimadoline did not. These results suggest that peripheral and central MOR and central KOR may be involved in the modulation of scratching behaviour in imiquimod-treated mice.

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