PubMed · 6514984
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1984. Antidepressant side effects.. https://pubmed.ncbi.nlm.nih.gov/6514984/
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The effectiveness of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were contrasted in endogenous/melancholic depression. By reviewing Hamilton Depression Rating data from controlled trials, the data indicate that TCAs are consistently more effective than the SSRIs. Despite the wide use of SSRIs in the treatment of depression, it seems reasonable that clinicians subtype their depressed patients and treat melancholic patients first with a course of TCAs. For melancholic patients who have not responded to a SSRI, pharmacotherapeutic alternatives include (1) a TCA alone; (2) TCA augmentation of the SSRI, or (3) lithium augmentation of the SSRI.
We performed an extensive pharmacological study of the 5-hydroxytryptamine (5-HT) transporter polypeptide cloned from human placenta. Transient expression of this 630 amino acid polypeptide in HeLa cells led to saturable 5-HT uptake activity (Km = 858 nM). This 5-HT uptake was blocked by selective 5-HT inhibitors, such as citalopram, litoxetine, sertraline, and indalpine, with Ki values in the low nanomolar range, and it exhibited a pharmacological profile similar to that found in rat brain. [3H]Citalopram binding to membrane preparations of the transfected cells occurred to a single class of high-affinity binding sites (Kd = 5.3 nM) and was potently inhibited by selective 5-HT uptake inhibitors. The pharmacological profile of [3H]citalopram binding to these transfected cells showed a good correlation with that of [3H]paroxetine binding to the rat cerebral cortical 5-HT transporter (r = 0.79). These data confirm that the full pharmacological characteristics of the 5-HT transport system are conferred by the expression of the 630 amino acid human placental 5-HT transporter polypeptide. [3H]Citalopram should, therefore, provide a useful probe for more insights at a molecular level into this cloned 5-HT transport system.