Interaction of the antipsychotic drugs with dopamine receptors of the D2, D3, or D4 subclasses is thought to be important for their mechanisms of action. Consideration of carefully defined affinities of the drugs for these three receptors suggests that occupancy of the D4 subclass is not mandatory for achieving antipsychotic effects, but actions at D2 or D3 receptors may be important. A major d...

Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D3...

dopamine D3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D3 receptor antagonist trans-N-[4-[2-(6-cyano-1,2,3,4-tetrahydroi...

Tetrahydroprotoberberine alkaloids have shown interesting polypharmacological actions at dopamine receptors and are a unique template from which to mine novel molecules with dual selective actions at D1 and D3 receptors. Such compounds will be valuable to evaluate as anti-cocaine therapeutics. Towards that eventual goal, we engaged an SAR study in which a series of C9 alkoxy analogues of the D1...

D2 and D3 dopamine receptors belong to the largest family of cell surface proteins in eukaryotes, the G protein-coupled receptors (GPCRs). Considering their crucial physiologic functions and their relatively accessible cellular locations, GPCRs represent one of the most important classes of therapeutic targets. Until recently, the only strategy to develop drugs regulating GPCR activity was thro...

T he dopamine D3 receptor is a member of the D2 family of dopamine receptors. Several investigators have suggested that D3 receptors are involved in the regulation of locomotion, in the pathophysiology of schizophrenia, and in drug abuse. Dopamine enhances basal and stimulus evoked release of arachidonic acid, as well as the production of one of its metabolites, prostaglandin E2 (PGE2), in CHO ...

T he dopamine D3 receptor is a member of the D2 family of dopamine receptors. Several investigators have suggested that D3 receptors are involved in the regulation of locomotion, in the pathophysiology of schizophrenia, and in drug abuse. Dopamine enhances basal and stimulus evoked release of arachidonic acid, as well as the production of one of its metabolites, prostaglandin E2 (PGE2), in CHO ...

Herein we report the synthesis and evaluation of a series of new pramipexole derivatives as highly potent and selective agonists of the dopamine-3 (D3 ) receptor. A number of these new compounds bind to the D3 receptor with sub-nanomolar affinity and show excellent selectivity (>10,000) for the D3 receptor over the D1 and D2 receptors. For example, compound 23 (N-(cis-3-(2-(((S)-2-amino-4,5,6,7...

BACKGROUND Although a correlation between the central dopaminergic system and intelligence may exist, the results from imaging studies remain inconclusive. The aim of this study was to explore the relationship between striatal dopamine D2/D3 receptor availability and verbal intelligence quotient (VIQ) using single photon emission computed tomography (SPECT). METHOD Striatal D2/D3 receptor ava...

In spite of intensive research, the problem of treating antidepressant-resistant depressive patients has not yet been solved. Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptors, amantadine (AMA), produced stronger "antidepressant" effect in the forced swimming test (Porsolt's test) ...