RATIONALE: Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported. OBJECTIVE: Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized. RESULTS: Antipsychotics exert efficacy without extrapyramidal side effects (EPS's) when their occupation of dopamine D2 receptors reaches 65-80%. When a "tightly binding" antipsychotic binds 70% of D2 receptors, the remaining 30% are available for endogenous dopamine to bind. These tight antipsychotics suppress dopamine transmission in both tonic/phasic components equally so that similar proportions are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In this condition, less than 10% of D2 receptors are available for endogenous dopamine to bind; however, EPS's do not occur because aripiprazole exerts partial dopaminergic agonistic activity. Because the concentration of aripiprazole in the brain is relatively constant and it binds to D2 receptors tightly, the added dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the phasic component relatively more than the tonic component. In contrast, under treatment with "loosely binding" antipsychotics, phasic dopaminergic transmission is relatively preserved. CONCLUSIONS: Tight antipsychotics suppress both tonic and phasic components equally. Aripiprazole suppresses the phasic component relatively more than the tonic; that is, aripiprazole is a phasic [corrected] component buster. By contrast, suppression of the phasic component by loosely binding antipsychotics may be relatively weak.
RATIONALE: Aripiprazole is a recently introduced antipsychotic with a unique pharmacological profile, a dopamine partial agonist. Dopaminergic neural transmission has two different components, tonic and phasic, which have different physiological functions, but the effects of aripiprazole on tonic and phasic components are not reported. OBJECTIVE: Studies on antipsychotics including aripiprazole and tonic/phasic dopamine transmission are summarized. RESULTS: Antipsychotics exert efficacy without extrapyramidal side effects (EPS's) when their occupation of dopamine D2 receptors reaches 65-80%. When a "tightly binding" antipsychotic binds 70% of D2 receptors, the remaining 30% are available for endogenous dopamine to bind. These tight antipsychotics suppress dopamine transmission in both tonic/phasic components equally so that similar proportions are kept. Aripiprazole is effective when >90% of D2 receptors are occupied. In this condition, less than 10% of D2 receptors are available for endogenous dopamine to bind; however, EPS's do not occur because aripiprazole exerts partial dopaminergic agonistic activity. Because the concentration of aripiprazole in the brain is relatively constant and it binds to D2 receptors tightly, the added dopaminergic agonism may show a tonic nature. Thus, aripiprazole suppresses the phasic component relatively more than the tonic component. In contrast, under treatment with "loosely binding" antipsychotics, phasic dopaminergic transmission is relatively preserved. CONCLUSIONS: Tight antipsychotics suppress both tonic and phasic components equally. Aripiprazole suppresses the phasic component relatively more than the tonic; that is, aripiprazole is a phasic [corrected] component buster. By contrast, suppression of the phasic component by loosely binding antipsychotics may be relatively weak.
Authors: Fuji Yokoi; Gerhard Gründer; Kathleen Biziere; Massoud Stephane; Ahmet S Dogan; Robert F Dannals; Hayden Ravert; Ajit Suri; Steven Bramer; Dean F Wong Journal: Neuropsychopharmacology Date: 2002-08 Impact factor: 7.853
Authors: Alessandra Benedetti; Antonello Di Paolo; Marianna Lastella; Francesco Casamassima; Chiara Candiracci; Antonella Litta; Laura Ciofi; Romano Danesi; Lorenzo Lattanzi; Mario Del Tacca; Giovanni Battista Cassano Journal: Clin Pract Epidemiol Ment Health Date: 2010-06-04
Authors: Charles B Mikell; Guy M McKhann; Solomon Segal; Robert A McGovern; Matthew B Wallenstein; Holly Moore Journal: Stereotact Funct Neurosurg Date: 2009-06-26 Impact factor: 1.875