The antinociceptive effect of DBO-83 (3-[6-Cl-pyridazin-3-yl]-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 non-stimulated 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.

Antinociceptive profile of the new nicotinic agonist DBO-83 / C. Ghelardini, N. Galeotti, D. Barlocco, A. Bartolini. - In: DRUG DEVELOPMENT RESEARCH. - ISSN 0272-4391. - 40:3(1997), pp. 251-258. [10.1002/(SICI)1098-2299(199703)40:3<251::AID-DDR5>3.0.CO;2-J]

Antinociceptive profile of the new nicotinic agonist DBO-83

D. Barlocco
Penultimo
;
1997

Abstract

The antinociceptive effect of DBO-83 (3-[6-Cl-pyridazin-3-yl]-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 non-stimulated 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.
Analgesia; Antinociception; Nicotinic agonist
Settore CHIM/08 - Chimica Farmaceutica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/189517
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