[Does 'selective binding profile' result in 'selective treatment'?].
It has been believed that the 'selective binding profile' may result in the 'selective treatment' for a disease. However, typical antipsychotics with the selective affinity for dopamine D2 receptor produce antipsychotic efficacy against positive symptoms accompanied with extrapyramidal side effects. Serotonin-dopamine-antagonists produce fewer EPS, since they have a potent antagonistic activity for 5-HT2A receptor besides the dopamine D2 antagonism. The disinhibition of diminished glutamatergic transmission and alpha 1 antagonism by MARTAs (Multi-Acting-Acting-Receptor-Targeted-Antipsychotics) can reduce positive symptoms of schizophrenic patients, and the 5-HT2A antagonitic and anticholinergic activities of the drugs may reduce the EPS. Moreover, MARTAs increase intracellular concentrations of dopamine and norepinephrine in the prefrontal cortex and disinhibit the diminished glutamatergic transmission, which are expected to improve the negative symptoms, anxiety and depressive symptoms, and cognitive impairment that are difficult to be treated by other existing antipsychotics. These important biological changes are induced by the antagonism of 5-HT2A, 5-HT2C, alpha 1-adrenergic and muscarinic receptors by MARTAs. Thus a multireceptorial profile of MARTA is considered to result in the improved treatment. Therefore 'selective binding profile' does not always mean 'selective treatment.' Instead, if a breakthrough drug is to be developed for the treatment of refractory diseases, it may be necessary to rethink the ordinary strategy targeting for a single receptor.
Suzuki
T
T
Department of Toxicology, School of Pharmacy, Hoshi University, 2-4-41, Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
D014150:Antipsychotic Agents / Q000627:therapeutic use*; D006801:Humans; D017448:Receptors, Dopamine D2 / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology*; D011985:Receptors, Serotonin / Q000502:physiology
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D011955:Receptors, Drug; D011985:Receptors, Serotonin