Abstract

/980Do TricyclicBY WILLIAMHEYDORN, ALAN FRAZER,PH.D.,AND JOETransmission?MENDELS, M.D.An UpdateThe centeredtnicyclic oneffects. Althoughmany ofpharmacologic beneficialhave multiple effects on monoaminergic critical question of what the net resultfects is on the transmission processsynapses. The of all these efremains unan-effects,the issuedoubt.cyclics’amines tamineInitially, attention was focused on the tnability to block the neunonal uptake of monolike norepinephrine (NE) or 5-hydroxytryp(senotonin, 5HT). This was observed in vitroafter acute administration of the drug related to ani-mals.of theof affectiveillphan-macologic observations; these theories suggested that the drugs act by overcoming a hypothesized aminergic deficiency (1). However, this approach failed to take into account the fact that antidepressants are given to patients over long periods oftime-weeks, months, and on occasion even years. This is important because we know now that the initial inhibitory effect of the drugs on amine uptake results in a variety of compensatory responses by monoamine neurons. These changes appear to attenuate the early potentiating” effects of the drugs. For example, at the level of the presynaptic neuron, the acute tnicyclic-induced block of monoamine reuptake causes fairly rapid decrements in the firing rate of both serotonin(2) and NE-containing (3) neurons as well as a reduction in the turnover of both of these brain amines (4, 5).