Effects of mianserin on noradrenergic mechanisms.
Mianserin increased stimulation-induced release of noradrenaline from guinea-pig atria and brain cortex slices. The increase still occurred when neuronal reuptake of noradrenaline was blocked by cocaine. Mianserin blocked the neuronal uptake of 3H-noradrenaline only in high concentrations (1 microM in atria produced 40% block; 10 microM in cortex produced 57% block). Lower concentrations (0.01 microM in atria; 1 microM in cortex) significantly increased stimulation-induced release of noradrenaline. It is concluded that increases in transmitter release from noradrenergic nerves produced by mianserin can be attributed to blockade of the alpha 2-adrenoceptors involved in autoinhibitory feedback mechanism at nerve terminals, rather than to blockade of neuronal reuptake of noradrenaline. This effect on noradrenergic transmission in the central nervous system could explain the antidepressant actions of mianserin in accordance with the hypothesis of Schildkraut.
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000378:metabolism*; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D014316:Tritium
D003984:Dibenzazepines; D014316:Tritium; D008803:Mianserin; D003042:Cocaine; D009638:Norepinephrine