Investigation of the synergistic effect of asenapine maleate with fluoxetine on ketamine induced behavioural effects and estimation of brain monoamine in rats

Abstract

Asenapine maleate (ASM), a potent antipsychotic for schizophrenia, has low oral bioavailability due to Cytochrome P450-1A2 metabolism and has been linked to depression side effects. Aim of the study is to investigate the effect of Asenapine Maleate-Fluoxetine combination. By decreasing CYP1A2, FLX could boost the bioavailability and effectiveness of ASM while reducing its side effects. The increased immobility time in ASM with FLX treated group compared to disease control while rearing and ambulation activities were significantly higher in the ASM, FLX, and combination compared to the disease control group, grooming was significantly lower in the ASM-treated and in the combination compared to the disease group. The Dopamine is significantly decreased in FLX and ASM with FLX treated group, the 5-Hydroxytryptamine is higher in all other groups except disease control and the noradrenaline concentration was higher in the ASM and ASM with FLX compared to the disease control group. The ASM and FLX show synergistic action, after dose, there is substantial cataleptic activity due to dopamine receptor blockade in the nigrostriatal pathway, causing muscular stiffness. Further research is required to prevent catalepsy and excessive diabetes induction due to the combination of ASM and FLX.

GRAPHICAL ABSTRACT

Keywords:

• Asenapine maleate
• Schizophrenia
• Fluoxetine
• Synergistic effect
• Behavioral tests
• Brain monoamine