Assessment the effect of Dapoxetine and/or Acetaminophen in rats; neurochemicals and oxidative stress biomarkers evaluation

Author:

Georgy Gehan S.1,Laila Ibrahim M. Ibrahim2,Amer Mohamed E.3,Mohammad F. Ebtehal1

Affiliation:

1. Pharmacology Department, Egyptian Drug Authority (EDA), Giza P.O. 29, Egypt.

2. Molecular Drug Evaluation Department, Egyptian Drug Authority (EDA), Giza P.O. 29, Egypt

3. Histology Department, Faculty of Medicine, Al‐ Azhar University, Damietta P.O. 11651, Egypt

Abstract

Dapoxetine is a newer anti‐depressant that is used for severe forms of depression via selective serotonin reuptake inhibition conduit. We aimed to evaluate the effect of different doses of dapoxetine lonely or with acetaminophen (AMP). Seven groups of albino rats were used where dapoxetine was administered orally at the doses of 3, 5, and 8 mg/kg body weight for a period of 14 days in groups 2, 4, and 6, respectively. AMP (67.5 mg/kg body weight) was co‐administered with dapoxetine (3, 5, and 8 mg/kg body weight) for 14 days in groups 3, 5 and 7, respectively. Dapoxetine in mid and high dose plus AMP increased body weight and hematological parameters. Ambulation and rearing were declined with mid and high doses of dapoxetine+AMP, contrary to grooming. Struggling was decreased with high doses of dapoxetine+AMP. High dose of dapoxetine+AMP induced lowering of serotonin and dopamine as well as increasing of cholinesterase. Brain derived neurotrophic factor was decreased in all groups. Oxidative stress biomarkers were augmented with high dose of dapoxetine+AMP. High doses of dapoxetine and/or AMP induced loss of the Purkinje cell layer at cerebellum. The high dose of dapoxetine+AMP denotes behavioral, histopathological and neurochemical alterations, even though no serotonin syndrome occurs.

Publisher

Tsinghua University Press

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