Antidepressant agents protriptyline

Compounds in this dibenzocycloheptene series also manifest antidepressant activity when the trigonal one-carbon bridge is replaced by tetrahedral carbon. Thus, the reaction of hydrocarbon (24-7) with a metal amide in liquid ammonia leads to the corresponding carbanion (29-1). Treatment of that with the ethyl carbamate from A -methyl-3-chloropropylamine (29-2) leads to the alkylation product. The carbamate protecting group is then removed by sequential saponification with a base followed by acidification. This yields the antidepressant agent protriptyline (29-3) [30]. 

Fluoxetine is a selective serotonin-reuptake inhibitor (SSRI) that produces a net increase in (post-synaptic motor neuron) serotonin delivery after 4-6 weeks of use. A double-blind, randomized cross-over trial compared fluoxetine to the tricyclic antidepressant agent protriptyline and placebo in 12 patients with sleep-disordered breathing [52], The group apnea-hypopnea index (AHI) improved with fluoxetine compared to placebo, but there was great variability of response and other measures of disordered sleep did not change. These potentially beneficial results in a small number of patients need to be replicated in well-designed larger studies to support a useful role in clinical practice. 

These result from the drug s sympathoplegic actions. The major adverse effect is postural hypotension. This effect can be almost totally prevented by concomitant administration of a tricyclic antidepressant agent such as protriptyline. Nausea and vomiting may occur after the intravenous administration of a bolus of bretylium. 

Clinically, protriptyline is a purer type of antidepressant agent, in that it lacks the sedative properties of amitriptyline and nortriptyline. It is said to be the more potent of the three agents and useful also in the treatment of anxiety depressions. However, until further clinical work is published, it will be difficult to assess the therapeutic spectrum of this most recent agent. 

CNS and cardiovascular actions of d,l-methylphenidate could theoretically be enhanced by combination with agents that block norepinephrine reuptake, such as the tricyclic antidepressants desipramine or protriptyline, venlafaxine, duloxetine, atomoxetine, milnacipran, and reboxetine... 

Be aware that among this class of agents (tri cy cl I c/tet racy cl ic antidepressants), protriptyline has uniquely low dosing (15-40 mg/day for profripfyline compared to 75-300 mg/day for mosf ofher tri cy cl I c/tet racy cl I c antidepressants)... 

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