In vivo occupancy of the 5-HT1A receptor by a novel pan 5-HT1(A/B/D) receptor antagonist, GSK588045, using positron emission tomography.

5-hydroxytryptamine 1 (5-HT1) receptor blockade in combination with serotonin reuptake inhibition may provide a more rapid elevation of synaptic 5-HT compared to serotonin reuptake alone, by blocking the inhibitory effect of 5-HT1 receptor activation on serotonin release. GSK588045 is a novel compound with antagonist activity at 5-HT1A/1B/1D receptors and nanomolar affinity for the serotonin transporter, which was in development for the treatment of depression and anxiety. Here we present the results of an in vivo assessment of the relationship between plasma exposure and 5-HT1A receptor occupancy.

Aripiprazole and its human metabolite are partial agonists at the human dopamine D2 receptor, but the rodent metabolite displays antagonist properties.

Aripiprazole is a novel antipsychotic drug, which displays partial agonist activity at the dopamine D(2) receptor. Aripiprazole has been extensively studied pre-clinically, both in vitro and in vivo, and these results have been correlated with clinical findings. However, aripiprazole is metabolised differently in rats and man and these metabolites may contribute to the profile of aripiprazole observed in vivo.

Pharmacological profile of antipsychotics at monoamine receptors: atypicality beyond 5-HT2A receptor blockade.

Antipsychotic drugs (APD) are widely prescribed for the treatment of schizophrenia. The APD are differentiated into typical and atypical based on the lower incidence of extra-pyramidal side-effects associated with the newer atypical APD. It was suggested that atypicality may arise from an interaction with the 5-hydroxytryptamine (5-HT)(2) receptor and specifically on the 5-HT(2):dopamine D(2) affinity ratio.

Therapeutic potential of serotonin antagonists in depressive disorders.

Although the precise neurochemical imbalances in depression are still unknown, a role for the neurotransmitter 5-hydroxytryptamine (serotonin) has been implicated since the identification of the first effective antidepressants, imipramine and iproniazid. This led to the development of the selective serotonin re-uptake inhibitors which are widely used in the treatment of depression and depressive disorders, including generalised anxiety disorder, social phobia, obsessive compulsive disorder etc. Studies involving chronic administration in rats led to the hypothesis that the different classes of antidepressant treatment produce a common neuroadaptive change, namely an enhancement of serotonin neurotransmission, albeit via different pre and postsynaptic mechanisms.