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Serotonin receptors and site-selective agents

100%

Gelennon R. A.

nr 1

Few site-selective serotonergic agents are currently available; in fact, most of these agents might more appropriately be termed semi-selective in that they typically bind to at least two different populations of serotonin receptors. We describe the application of structure-affinity relationship (SAFIR) studies to the development of high- affinity and/or site-selective serotonergic agents; examples are provided from work conducted in our laboratories. Also discussed is the concept of selectively non-selective agents and their potential preclinical and clinical utility. A case is made for development of selective and nonselective serotonergic agents.

Involvement of some 5-HT receptors in methamphetamine-induced locomotor activity in mice

84%

Ginawi O. T. , Al-Majed A. A. , Al-Suwailem A. K. , El-Hadiyah T. M. H.

nr 2

Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was signficantly antagonized by NAN-190 ( 5-HT1A antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT1B/1D antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT2C antagonist) at a dose of 8mg/kg, IP. On the other hand, methysergide ( 5-HT 2A/2B antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT3 antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT 1A, 5-HT 1B/1D and/or 5-HT2C receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT 2A/2B and/or 5-HT3 receptor subtypes may result in decreased activity.