Maprotiline hydrochloride (Psymion) is a bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use.

Maprotiline inhibits HERG channels expressed in HEK cells with an IC50 of 5.2 μM and HERG channels expressed in oocytes with an IC50 of 24 μM. Maprotiline blocks open channels but has no significant effect on closed channels. [1] Maprotiline is atetracyclic antidepressant, which strongly inhibits the uptake of noradrenaline, though it is notable in its lack of inhibition of serotonergic uptake. Maprotiline also has markedly less pronounced alpha-adrenergic blocking activity than amitriptyline. [2] Maprotiline decreases cell viability in a concentration- and time-dependent manner in Neuro-2a cells. Maprotiline induces apoptosis and increases caspase-3 activation. Maprotiline also induces [Ca(2+)](i) increases which involves the mobilization of intracellular Ca(2+) stored in the endoplasmic reticulum. [3]

Maprotiline results in significantly increases GluR1 and GluR2/3 subunit expression in the nucleus accumbens and dorsal striatum of mice as detected by immunohistochemistry; and significantly increases GluR1 and GluR2/3 expression in the hippocampus, as demonstrated by Western blot analysis. [4] Maprotiline has a potent anti-inflammatory effect in rats and this effect is linked to the peripheral and supraspinal actions of the drug. [5] Maprotiline impairs learning when administered before training, but no statistically significant effect is evident when administered after training. [6]