Interaction of antidepressants with 4-aminopyridine.
Systemic administration of 4-Aminopyridine at a dose of 4 mg/kg (4-AP) induces hypothermia in mice. Scopolamine (ED50 = 0.26 mg/kg) and two tricyclic antidepressants, desipramine (ED50 = 1.82 mg/kg) and IM/P/3/4 (ED50 = 8.95 mg/kg) completely antagonize 4-AP-induced hypothermia, whereas minaprine (0.1-0.25 mg/kg), a non-tricyclic antidepressant, reverts only 45% of the maximal effect of 4-AP. Oxotremorine at a dose of 0.05 mg/kg (OXO) induces a hypothermic effect comparable to that of 4-AP. Scopolamine (ED50 = 0.011 mg/kg) completely reverts OXO-induced hypothermia whereas desipramine and IM/P/3/4 never produce more than 60% of antagonism over a wide range of doses. Minaprine does not affect OXO-induced hypothermia. These results suggest that the interaction of antidepressants with cholinergic function occurs mainly at the pre-synaptic level.
Volterra
G
G
Pharmacological Research Department A. Menarini Pharmaceuticals, Florence, Italy.
Lecci
A
A
D015761:4-Aminopyridine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D003080:Cold Temperature; D003891:Desipramine / Q000494:pharmacology*; D007036:Hypothermia, Induced; D008297:Male; D051379:Mice
D000929:Antidepressive Agents, Tricyclic; D015761:4-Aminopyridine; D000109:Acetylcholine; D003891:Desipramine