The Use of LeuT as a Receptor Model for Antidepressant Development

Lina Rustanti
Journal article Health Science Journal of Indonesia • December 2010


Selective serotonin re-uptake inhibitors (SSRIs) have been considered to be promising drugs in psychiatric practice because of their selectivity to serotonin re-uptake transporter (SERT). Sertraline and fluoxetine are considered to be effective SSRIs as their ability in binding SERT and inhibit neurotransmitter recycling. However, they also bind norepinephrine and dopamine transporter (NAT and DAT) that cause undesirable effects. Thus, the study of drug-receptor interaction between SSRIs and SERT is important to gauge the active site of the drugs. By using Leucine Transporter (LeuT) from Aquifexaeolicusas a SERT model, the mode of SSRIs-SERT interaction was revealed. Nonetheless, it is uncertain whether the drugs that bind to LeuT would be effective to human SERT because of the high evolutionary convergence between them. Halogenbinding pocket (HBP) was found to be the key determinant in the drug-receptor interaction. LeuT has ~25% sequence similarity to human SERT with highly conserved amino acid sequences in the active site of these receptors, in which HBP is located. LeuT as the receptor model revealed the interaction between drugs and receptors. All these findings are very useful to develop more selective antidepressant medicines. (Health Science Indones 2010; 1: 51 - 57)




Health Science Journal of Indonesia

Health Science Journal of Indonesia is a journal published by the National Institute of Health Re... see more