Attenuated stress-induced catecholamine release in mice lacking the vasopressin V1b receptor.

Vasopressin V(1b) receptor is specifically expressed in the pituitary and mediates adrenocorticotropin release, thereby regulating stress responses via its corticotropin releasing factor-like action. In the present study we examined catecholamine release in response to two types of stress in mice lacking the V(1b) receptor gene (V(1b)R(-/-) mice) vs. wild-type mice.

In vitro profile of the antidepressant candidate OPC-14523 at rat and human 5-HT1A receptors.

This study determined the in vitro functional profile of 1-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-5-methoxy-3,4-dihydro-2-quinolinone monomethanesulfonate (OPC-14523) at rat and human serotonin (5-HT) 5-HT1A receptors and binding affinity of OPC-14523 at human frontocortical 5-HT1A receptors. OPC-14523 (1 microM) increased guanosine-5'-O-(3-[35S]thio)-triphosphate ([35S]GTPgammaS) binding to 5-HT1A receptor-containing regions of rat brain tissue sections (approximately 53% of the effect of 1 microM (+)8-hydroxy-2-(di-n-propylamino)tetralin ((+)8-OH-DPAT) that were blocked by the selective 5-HT1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY-100635). OPC-14523 also behaved as a partial agonist in its stimulation of [35S]GTPgammaS binding to membranes from rat hippocampus (pEC50=7.

Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic.

Aripiprazole is the first clinically approved atypical antipsychotic agent having dopamine D2 receptor partial agonist activities. To evaluate aripiprazole's agonist and antagonist properties, we established a Chinese hamster ovary cell line expressing high and low densities of the long and short isoforms of human dopamine D2 receptors, then compared its properties with 7-{3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy}-2(1H)-quinolinone (OPC-4392), S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP), and terguride (other partial agonists) using forskolin-stimulated cAMP accumulation as an index. In cells expressing high receptor densities, all partial agonists predominantly behaved as agonists.

The novel antipsychotic aripiprazole is a partial agonist at short and long isoforms of D2 receptors linked to the regulation of adenylyl cyclase activity and prolactin release.

Aripiprazole is a novel antipsychotic with a unique mechanism of action, which differs from currently marketed typical and atypical antipsychotics. Aripiprazole has been shown to be a partial agonist at the D(2) family of dopamine (DA) receptors in biochemical and pharmacological studies. To demonstrate aripiprazole's action as a partial D(2) agonist in pituitary cells at the molecular level, we retrovirally transduced the short (D(2S)) and the long (D(2L)) form of the human DA D(2) receptor gene into a rat pituitary cell line, GH4C1.

In vivo effects of aripiprazole on cortical and striatal dopaminergic and serotonergic function.

In vivo microdialysis was used to monitor the effects of oral aripiprazole and olanzapine on basal extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA) in the medial prefrontal cortex and striatum of conscious, freely moving rats. Acute aripiprazole administration did not affect dopamine output, but produced moderate increases in DOPAC and HVA concentrations, in medial prefrontal cortex or striatum of drug-naïve rats. Similarly, aripiprazole did not affect dopamine output but produced moderate elevations in DOPAC and HVA concentrations in the striatum of chronic aripiprazole-pretreated rats.