SA14867, a newly synthesized kappa-opioid receptor agonist with antinociceptive and antipruritic effects
| Autor: | Yaeko Tsukahara-Ohsumi, Masashi Niwa, Minoru Sasano, Hiroyuki Aono, Fumio Tsuji, Naoki Inagaki, Mikiko Nakamura, Keiko Mizutani |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Agonist Leukotrienes medicine.drug_class Analgesic Receptors Opioid mu Pharmacology κ-opioid receptor Receptors Opioid delta medicine Animals Humans Rats Wistar Tartrates Antipruritic Pain Measurement Analgesics Dose-Response Relationship Drug Morphine business.industry Receptors Opioid kappa Antipruritics Receptor antagonist Macaca mulatta Rats Analgesics Opioid Thiazoles Hyperalgesia Asimadoline Tramadol medicine.symptom business medicine.drug |
| Zdroj: | European Journal of Pharmacology. 647:62-67 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2010.08.012 |
| Popis: | SA14867 ((+)-3-Acetyl-6-chloro-2-[2-(3-(N-(2-ethoxyethyl)-N-isopropylamino)propoxy)-5-methoxyphenyl]benzothiazoline O,O'-diacetyl-L-tartrate), a selective kappa-opioid receptor agonist, was synthesized and its antinociceptive and antipruritic effects were investigated. In a functional binding assay, SA14867 showed approximately more than 31,000 and 2200 fold higher affinity for the kappa-opioid receptor than for the mu- and delta-opioid receptors, respectively. SA14867 inhibited acetic acid-induced writhing and formalin test results after oral administration. The ED(50) values of SA14867 for acetic acid-induced writhing and for formalin test first phase and second phase were 1.9, 9.4, and 6.4 mg/kg, respectively. These values were smaller than those of asimadoline, U-50488H, and tramadol. SA14867 also showed antinociceptive effects in silver nitrate-induced arthritis that were as strong as U-50488H, tramadol, and morphine, and were stronger than asimadoline. The ED(50) value of SA14867 for hyperalgesia of arthritis was approximately 10 mg/kg. In addition, SA14867 showed antipruritic effects on 5-hydroperoxyeicosatetraenoic acid (HPETE) and substance P-induced pruritic models at 1 to 3 mg/kg. SA14867 also attenuated scratching reactions in a morphine-induced pruritic model in monkeys. Some of the inhibitory effects of SA14867 on nociceptive and pruritic models were attenuated by a kappa-opioid receptor antagonist, nor-BNI. These results suggest that SA14867 is a potential antinociceptive and antipruritic drug. |
| Databáze: | OpenAIRE |
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