Molecular mechanisms in the action of minaprine.
1. Minaprine is a pyridazine derivative endowed with antidepressant activity, however biochemical studies following repeated administrations are still lacking. 2. Rats were administered with minaprine (10 mg/kg i.p.) twice daily for 3 weeks. 3. In minces from the frontal cortex of rats receiving minaprine the NE-induced cAMP accumulation is reduced suggesting that, similarly to other antidepressant treatments, minaprine attenuates the beta-adrenergic receptor function. 4. The selective lesion of the serotonergic axons abolished such attenuation. 5. In synaptic plasma membranes prepared from rats repeatedly treated with pargyline (at doses which block MAO tipo A and B) but not with minaprine, the number of 5HT1C and 5HT2 receptors was reduced. 6. Repeated administrations of minaprine but not of pargyline increased the Bmax values of [3H]-imipramine binding. In 5, 7-DHT lesioned rats minaprine failed to increase the number of the residual [3H]-imipramine recognition sites. 7. The authors conclude that the increase in the number of [3H]-imipramine recognition sites is unrelated to the IMAO activity of minaprine. 8. The presence of 5HT axons on which [3H]-imipramine recognition sites are located is an absolute requirement for the clinical efficacy of minaprine. 9. The action of minaprine in the regulation of the synthesis and/or of the release of an endogenous substance that is important in mediating brain beta-adrenergic function is discussed.
Gandolfi
O
O
Institute of Pharmacology, University of Bologna, Italy.
Roncada
P
P
Dall'Olio
R
R
Montanaro
N
N
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012016:Reference Values; D013570:Synaptic Membranes / Q000378:metabolism
D000928:Antidepressive Agents; D011724:Pyridazines; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C006149:minaprine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases