Antinociception induced by amitriptyline and imipramine is mediated by alpha2A-adrenoceptors.
The involvement of alpha2-adrenoceptors in the antinociception induced by the tricyclic antidepressants amitriptyline and imipramine was investigated in mice by using the hot-plate and abdominal constriction tests. The antinociception produced by amitriptyline (15 mg/kg, i.p.) and imipramine (15 mg/kg, i.p.) was prevented by reserpine (2 mg/kg, i.p.) and yohimbine (3-10 mg/kg, i.p.) but not by naloxone (1 mg/kg, i.p.), atropine (5 mg/kg, i.p.), CGP 35348 (100 mg/kg, i.p.) and prazosin (1 mg/kg, i.p.). On the basis of the above data, it can be postulated that amitriptyline and imipramine exerted their antinociceptive effect by activation of alpha2-adrenoceptors. Administration of the alpha2A-adrenoceptor antagonist BRL 44408 (1 mg/kg, i.p.) prevented amitriptyline and imipramine antinociception, whereas the alpha2B/C-adrenoceptor antagonist ARC 239 (10 mg/kg, i.p.) was ineffective. These data indicate that the enhancement of the pain threshold produced by amitriptyline and imipramine is mediated by activation of alpha2A-adrenoceptors. Neither tricyclic antidepressants nor the antagonists used impaired mouse performance evaluated by the rota-rod and hole-board tests.
Ghelardini
C
C
Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.
Galeotti
N
N
Bartolini
A
A
D000639:Amitriptyline / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D000929:Antidepressive Agents, Tricyclic; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D009943:Organophosphorus Compounds; D018341:Receptors, Adrenergic, alpha-2; D000639:Amitriptyline; D015016:Yohimbine; D009270:Naloxone; C066430:CGP 35348; D007099:Imipramine; C072125:BRL 44408