Maprotiline, a tetracylic compound, and the large group of tricylic antidepressants ( Table, ...1) effectively treat the neurovegetative signs of depression. Potential sites of action are at the level of receptors (desensitization of presynaptic a 2-receptors, subsensitivity of b-adrenergic receptors), reuptake transporters (block of monoamine reuptake), and intracellular second-messenger systems.
Table 1 Treatment indices and side-effect profiles of common antidepressants
The cyclic compounds do not have significantly different efficacy in treating depression but do show a variety of side-effect profiles. Adverse effects are closely related to their chemical structure and their affinity for postsynaptic receptors. Amitriptyline, clomipramine, and doxepin have a high affinity for muscarinic cholinergic receptors and cause more anticholinergic side-effects (dryness of mouth, blurred vision, constipation, urinary retention) than the other cyclic compounds. Sedation and orthostatic hypotension are two other side-effects that occur frequently with some, but not all, cyclic antidepressants. The ability of cyclic antidepressants to interfere with normal cardiac conduction and potentially lead to lethal cardiac arrhythmias makes them dangerous in the hands of suicidal patients.
Use of clomipramine improves both depression and obsessive-compulsive disorder. Amoxapine, which blocks dopamine D2 receptors and has moderate neuroleptic activity, can be used to treat patients with psychotic depression, but its use carries the risk of extrapyramidal side-effects.
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