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Year : 2012  |  Volume : 2  |  Issue : 3  |  Page : 223-228

Evaluation of antinociceptive/analgesic activity of SSRIs (fluoxetine and escitalopram) and atypical antidepressants (venlafaxine and mirtazapine): An experimental study

1 Department of Pharmacology, LLRM Medical College, Meerut, India
2 Department of Pharmacology, MLB Medical College, Jhansi, India
3 Department of Oral Pathology and Microbiology, ITS-CDSR, Muradnagar, Ghaziabad, Uttar Pradesh, India

Correspondence Address:
Pranav Sikka
Department of Pharmacology, LLRM Medical College, Meerut, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2231-0738.99474

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Objective: To evaluate the antinociceptive/analgesic action of selective serotonin reuptake inhibitors (SSRIs; fluoxetine, escitalopram) and atypical antidepressants (mirtazapine, venlafaxine) and to delineate their probable mechanism. Materials and Methods: The study was conducted on albino mice (25-35 g) and Wistar rats (80-100 g) of either sex. Different doses of morphine (0.5 and 1 mg/kg), fluoxetine (2, 5, and 10 mg/kg), venlafaxine (30, 40, and 50 mg/kg), mirtazapine (3, 5, and 7 mg/kg), and escitalopram (2.5, 5, and 10 mg/kg) were administered subcutaneously in order to ascertain their subanalgesic doses using tail flick analgesiometer and writhing method. Tail flick latencies were obtained at 15, 30, 60, and 120 min after drug administration. In another set of experiments, abdominal writhing was produced by employing 4% saline (1 ml/kg; i.p.) as irritant. Pretested sensitive rats were given test drugs 10 min before saline injection and abdominal writhing was noted between 30 seconds and 3 min of administering saline. Naloxone (1 mg/kg) was administered 10 min prior to test drug for testing antagonism in both sets of experiments. Results: In both sets of experiments, fluoxetine (5 and 10 mg/kg), mirtazapine (5 and 7 mg/kg), and venlafaxine (40 and 50 mg/kg) were found to have antinociceptive activity, but not at lower doses. Escitalopram failed to show antinociceptive activity at any of the doses used. The antinociceptive effect of all the drugs was antagonized by naloxone. Further, subanalgesic doses of fluoxetine, mirtazapine, and venlafaxine showed analgesic activity with suboptimal dose of morphine (0.5 mg/kg). Conclusion: Fluoxetine, mirtazapine, and venlafaxine have antinociceptive activity, whereas escitalopram does not have; their site of action seems to be the same as that of opioid analgesics ("mu" receptors). However, involvement of other pathways (cholinergic, histaminic, noradrenergic, GABAergic) cannot be excluded in mediation of their analgesic activity, which requires further elucidation.

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