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Citalopram, a selective serotonin reuptake inhibitor (SSRI), is used as a neuroendocrine probe in human subjects to assess serotonin (5-hydroxytryptamine; 5-HT) function as reflected in prolactin and plasma cortisol release. Citalopram is a racemic mixture of equal parts of the S(+) and R(-) enantiomers. The S(+) form ("escitalopram") has been identified as being the active isomer and inhibitor of serotonin reuptake and consequently antidepressant activity is associated almost exclusively with the S-enantiomer. Escitalopram has been shown to be approximately twice as potent as citalopram at the primary, high-affinity binding site on the human serotonin transporter. Interestingly, investigations have suggested an antagonistic interaction of the R- and S-enantiomer at an allosteric binding site on the serotonin transporter. This antagonism has been shown in animal studies where the addition of R-citalopram to escitalopram treatments significantly counteracts the antidepressant and anti-anxiolytic effects of escitalopram. From these clinical and experimental data, the researchers can anticipate that escitalopram would increase cortisol and prolactin in the neuroendocrine challenge paradigm more effectively than citalopram.
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