Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies

  title={Interaction of the novel antipsychotic aripiprazole with 5-HT1A and 5-HT2A receptors: functional receptor-binding and in vivo electrophysiological studies},
  author={Arlene D. Stark and Shaun Jordan and Kelly Ann Allers and Robert L. Bertekap and Ruoyan Chen and Tanaz Mistry Kannan and Thaddeus F. P. Molski and Frank D. Yocca and Trevor Sharp and Tetsuro Kikuchi and Kevin D. Burris},
BackgroundAripiprazole (7-{4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy}-3,4-dihydro-2(1H)-quinolinone) is a novel antipsychotic with a mechanism of action that differs from current typical and atypical antipsychotics. Aripiprazole interacts with a range of receptors, including serotonin [5-hydroxytryptamine (5-HT)] and dopamine receptors.Materials and methodsThis study examined aripiprazole’s interactions with 5-HT systems in vitro and in vivo to further clarify its pharmacologic properties… 

Acute Effects of Brexpiprazole on Serotonin, Dopamine, and Norepinephrine Systems: An In Vivo Electrophysiologic Characterization

In conclusion, the in vivo action of brexpiprazole on monoamine targets relevant in the treatment of depression and schizophrenia is assessed and α1- and α2-adrenergic receptors are evaluated.

Investigating the Potential Role of Serotonin-2B Receptor Antagonism in the Neuronal Actions of Adjunctive Aripiprazole

5-HT2B receptor blockade rescues an SSRI-mediated decrease in DA firing activity and increases mPFC pyramidal neuron firing and bursting activity mediated by aripiprazole and in combination with escitalopram may be, at least partly, moderated by 5- HT2B receptors expressed in this brain area.

Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties

Compounds possessing “balanced” 5- HT1A receptor agonism and D2 antagonism and, in some cases, combined with other beneficial properties, such as 5-HT2A receptor antagonism, are efficacious in a broad range of rodent pharmacological models yet have a lower propensity to elicit EPS or metabolic dysfunction.

WS-50030 [7-{4-[3-(1H-inden-3-yl)propyl]piperazin-1-yl}-1,3-benzoxazol-2(3H)-one]: A Novel Dopamine D2 Receptor Partial Agonist/Serotonin Reuptake Inhibitor with Preclinical Antipsychotic-Like and Antidepressant-Like Activity

Activity in preclinical models predictive of antipsychotic- and antidepressant efficacy similar to aripiprazole is shown, suggesting potential efficacy of WS-50030 versus positive and negative symptoms of schizophrenia, comorbid mood symptoms, bipolar disorder, major depressive disorder, and treatment-resistant depression.

Distinct electrophysiological effects of paliperidone and risperidone on the firing activity of rat serotonin and norepinephrine neurons

The capacity of paliperidone to reverse the selective serotonin reuptake inhibitor (SSRI)-induced inhibition of NE neuronal firing, without interfering with the effect of SSRIs of 5-HT neuronal activity, suggests that palipersidone may be a very effective adjunct in SSRI-resistant depression.



Short communication The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT 1A receptor

Aripiprazole is the first dopamine–serotonin system stabilizer, according to a study demonstrating potent, partial agonism at 5-HT1A receptors in a guanosine-5VO-(3-[35 S]thio)-triphosphate ([ 35 S]GTPgS)-binding assay.

The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor.

Effects of the novel antipsychotic agent 7-(4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy)-3,4-dihydro -2(1H)-quinolinone (OPC-14597) on prolactin release from the rat anterior pituitary gland.

The results suggest that OPC-14597 has a mixed agonist/antagonist profile at D2 receptors on lactotroph cells and thereby exerts either an antagonistic or an agonistic action, depending on the preexisting tone of the dopaminergic neuronal activities.

Receptor reserve for 5-hydroxytryptamine1A-mediated inhibition of serotonin synthesis: possible relationship to anxiolytic properties of 5-hydroxytryptamine1A agonists.

The results suggest that 5- HT1A receptor-mediated regulation of 5-HT synthesis appears to be mediated by somatodendritic autoreceptors on5-HT neurons in the midbrain raphé nuclei, and suggest that these autoreceptor possess a large receptor reserve for agonists.

Agonist and antagonist actions of antipsychotic agents at 5-HT1A receptors: a [35S]GTPgammaS binding study.

Recombinant human (h) 5-HT1A receptor-mediated G-protein activation was characterised in membranes of transfected Chinese hamster ovary cells by use of guanosine-5'-O-(3-[35S]thio)-triphosphate ([ 35S]GTPgammaS binding) to evaluate the efficacy and potency of agonists and antagonists at recombinant human 5- HT1A receptors.

Aripiprazole, a Novel Antipsychotic, Is a High-Affinity Partial Agonist at Human Dopamine D2 Receptors

These results, together with previous studies demonstrating partial agonist activity at serotonin 5-hydroxytryptamine (5-HT)1A receptors and antagonist activity at 5-HT2A receptors, support the identification of aripiprazole as a dopamine-serotonin system stabilizer.

Aripiprazole, A Novel Atypical Antipsychotic Drug with a Unique and Robust Pharmacology

The results support the hypothesis that the unique actions of aripiprazole in humans are likely a combination of ‘functionally selective’ activation of D2 (and possibly D3)-dopamine receptors, coupled with important interactions with selected other biogenic amine receptors—particularly 5-HT receptor subtypes (5-HT1A, 5- HT2A).