Jul 28, 2019

Lurasidone inhibits NMDA receptor antagonist-induced functional abnormality of thalamocortical glutamatergic transmission via 5-HT7 receptor blockade

British Journal of Pharmacology
Motohiro OkadaYuto Ueda

Abstract

Lurasidone is an atypical mood-stabilizing antipsychotic with a unique receptor-binding profile, including 5-HT7 receptor antagonism; however, the detailed effects of 5-HT7 receptor antagonism on various transmitter systems relevant to schizophrenia, particularly the thalamo-insular glutamatergic system and the underlying mechanisms, are yet to be clarified. We examined the mechanisms underlying the clinical effects of lurasidone by measuring the release of l-glutamate, GABA, dopamine, and noradrenaline in the reticular thalamic nucleus (RTN), mediodorsal thalamic nucleus (MDTN) and insula of freely moving rats in response to systemic injection or local infusion of lurasidone or MK-801 using multiprobe microdialysis with ultra-HPLC. Systemic MK-801 (0.5 mg·kg-1 ) administration increased insular release of l-glutamate, dopamine, and noradrenaline but decreased GABA release. Systemic lurasidone (1 mg·kg-1 ) administration also increased insular release of l-glutamate, dopamine, and noradrenaline but without affecting GABA. Local lurasidone administration into the insula (3 μM) did not affect MK-801-induced insular release of l-glutamate or catecholamine, whereas local lurasidone administration into the MDTN (1 μM) inhibited MK-8...Continue Reading

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References

Mentioned in this Paper

Schizophrenia
Catecholamine [EPC]
Entire Thalamic Reticular Nucleus
Molecular_function
HTR7
Injection Procedure
Lurasidone
Serotonin 7 receptor
Administration Procedure
Excitatory Amino Acid Antagonists

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