Mirtazapine displays marked affinity for cloned, human alpha2A-adrenergic (AR) receptors at which it blocks noradrenaline (NA)-induced stimulation of guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]-GTPgammaS) binding. Mirtazapine shows high affinity for cloned, human serotonin (5-HT)2C receptors at which it abolishes 5-HT-induced phosphoinositide generation. Mirtazapine markedly elevates dialysate levels of NA and, in FCX, DA, whereas 5-HT is not affected.[1] Mirtazapine enhances the effectiveness of the electrical stimulation of the ascending 5-HT pathway by blocking both alpha-2 adrenergic auto- and heteroreceptors. Mirtazapine blocks the suppressant effect of microiontophoretically applied norepinephrine (NE) on the firing activity of CA3 dorsal hippocampus pyramidal neurons, indicating their antagonistic effects on postsynaptic alpha-2 adrenoceptors. [2]

Mirtazapine (10-250 mg/kg i.v.) enhances dose-dependently the firing activity of the 5-HT neurons in naive rats, but not in 6-hydroxydopamine-pretreated rats. [2] Mirtazapine (5 mg/kg/day, s.c., using osmotic minipumps) increases the spontaneous firing activity of locus coeruleus noradrenaline (NA) neurons in male Sprague-Dawley rats. Mirtazapine antagonizes both the enhancing effect of a low dose (10 mg/kg, i.v.) and the reducing effect of a high dose (100 mg/kg, i.v.) of the alpha 2-adrenoceptor agonist clonidine on the effectiveness of the electrical stimulation of the ascending 5-HT pathway in suppressing the firing activity of dorsal hippocampus CA3 pyramidal neurons. [3] Mirtazapine (5 mg/kg s.c.) only slightly affects DOPAC and homovanillic acid levels in the striatum, hardly affects 5-HT release in freely moving rats, but clearly increased 5-hydroxyindole acetic acid. [4]