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Asian Journal of Biochemistry
  Year: 2014 | Volume: 9 | Issue: 1 | Page No.: 49-56
DOI: 10.3923/ajb.2014.49.56
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Differential Effect of Sumatriptan on Cerebellar 5-HT1B Receptors in Rat Brain
Rama Krishna Devaki and M.N. Subhash

Sumatriptan is a novel and highly effective drug against migraine and cluster headache attacks. This antimigraine drug is known to exert its effect through the modulation of serotonin (5-HT) mediated neurotransmission. 5-HT1B receptors in rats and 5-HT1D receptors in humans have been thought to be likely targets of sumatriptan. In the present study the effect of varying dose and duration of sumatriptan on the density of 5-HT1B receptors in the rat cerebellum were studied to understand its mechanism of action. Sprague Dawley rats were administered with different doses of sumatriptan (0.2-16 mg kg-1 b.wt. i.p.) for seven days and 2, 4 and 8 mg kg-1 of sumatriptan for 7, 14 and 21 days. The radioligand binding assays were performed in cerebellar membranes using [3H]5-HT. Treatment with different doses of sumatriptan for seven days showed a significant (p<0.0001) downregulation of 5-HT1B receptors in a dose dependent manner. A significant decrease in the density of 5-HT1B receptors was observed with 0.2 mg (45%), 0.5 mg (72%) and 1 mg (70%) of sumatriptan treatment, with a significant decrease (p<0.001) in Kd values. No further decrease in either the density or in the Kd values was observed with increasing doses of Sumatriptan from 2 to 16 mg kg-1 b.wt. The magnitude of decrease in the receptor density was more significant with a lower dose (2 mg) of sumatriptan for a prolonged period of exposure (21 days). However, such change was not observed with higher doses (4 and 8 mg kg-1). Furthermore, sumatriptan showed a higher affinity for 5-HT1B receptors with a Ki value of 9.4±0.9 nM, when compared to other agonists and antagonists. Taken together, these findings suggest that desensitization of 5-HT1B receptor is dose and time dependent, which may be an important factor underlying the mechanism of action of sumatriptan as an antimigraine drug.
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How to cite this article:

Rama Krishna Devaki and M.N. Subhash, 2014. Differential Effect of Sumatriptan on Cerebellar 5-HT1B Receptors in Rat Brain. Asian Journal of Biochemistry, 9: 49-56.

DOI: 10.3923/ajb.2014.49.56








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