Antinociceptive profile of the new nicotinic agonist DBO-83

✍ Scribed by Carla Ghelardini; Nicoletta Galeotti; Daniela Barlocco; Alessandro Bartolini

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 170 KB
• Volume: 40
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199703)40:3<251::aid-ddr5>3.0.co;2-j

✦ Synopsis

The antinociceptive effect of -diazabicyclo[3.2.1]octane) was examined in mice and rats by using the hot-plate, abdominal constriction, and paw-pressure tests. In both species, DBO-83 (10-20 mg/kg ip in the mouse; 10-20 mg/kg ip in the rat) produced significant antinociception, an effect that was prevented by mecamylamine (2-5 mg/kg ip) but not by atropine (5 mg/kg ip), naloxone (1 mg/kg ip), and CGP 35348 (100 mg/kg ip). DBO-83 antinociception is mediated by a central mechanism of action since it is also effective after icv injection (5-7.5 µg per mouse). By comparing the areas under the curve of several well-known analgesic drugs such as morphine, diphenhydramine, clomipramine, and ketorolac at the highest doses that did not produce overt behavioral side effects, the antinociceptive efficacy of DBO-83 (20 mg/kg ip) was found to be greater than that exerted by the reference drugs. In the antinociceptive dose range, DBO-83 did not impair mouse motor coordination, spontaneous motility, or inspection activity. In vitro experiments showed the ability of DBO-83 to evoke the contractions of nonstimulated guinea pig ileum and the shift to the right of the DBO-83 concentration-response curve by mecamylamine (10 -5 M). On the basis of the above data, it can be postulated that DBO-83 exerted an antinociceptive effect mediated by a central nicotinic activation.