The Role of HTS

Macarron, R (2006) Critical review of the role of HTS in drug discovery. Drug Diseov Today 11, 277-279. 

Currently, hopes for compounds with greater clinical efficacy and faster onset of action than buspirone rest on the development of selective ligands for 5-HT receptors. So far, antagonists of 5-HT2a/c (e-g- ritanserin), 5-HTs (e.g. ondansetron) and 5-HT4 (e.g. zacopride) receptors have all been explored but their anti-anxiety effects are, at best, equivocal. Full appraisals of the role of 5-HT systems in anxiety and the actions of anti-anxiety drugs are to be found in Handley (1995), Barnes and Sharp (1999) and Olivier, van Wijngaarden and Soudijn (2000). 

Cali JP, Mears TW, Michaelis RE, Reed WP, Seward RW, Stanley CL, Yolken HT, and Ku HH (1975) The role of standard reference materials in measurement systems. NBS Monograph 148, Washington DC. 

The possible role of DA in the MDMA-indueed alterations of the serotonergie system was then examined. Teehniques previously used in studying the role of DA in the METH-indueed neuroehemieal effeets were employed. When DA synthesis was inhibited with MT, the effeet of multiple doses of MDMA on TPH activity (figure 6) and eoneentrations of 5-HT and 5-HIAA was attenuated. The degree of proteetion with MT seemed to be a funetion of the size and number of doses of MDMA used as well as a funetion of the serotonergie parameter that was measured. 

HT model. GAD symptoms may reflect excessive 5-HT transmission or overactivity of the stimulatory 5-HT pathways. Patients with SAD have greater prolactin response to buspirone challenge, indicating an enhanced central serotonergic response. The role of 5-HT in panic disorder is unclear, but it may have a role in development of anticipatory anxiety. Preliminary data suggest that the 5-HT and 5-HT2 antagonist meta-chlorophenylpiperazine causes increased anxiety in PTSD patients. 

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