AI Article Synopsis
- Naftidrofuryl is a peripheral vasodilator used for treating intermittent claudication and dementia, and interacts with the 5-HT(2A) receptor.
- The study aimed to evaluate naftidrofuryl's binding affinity and functional potency compared to sarpogrelate, revealing that its affinity is significantly lower at both the wild-type and mutant receptors.
- Additionally, naftidrofuryl demonstrated reduced inverse agonist activity compared to sarpogrelate, which may help clarify how it interacts with 5-HT(2A) receptors.
Article Abstract
Naftidrofuryl is a peripheral vasodilator that has been clinically used in the treatment of intermittent claudication and dementia. It has 5-hydroxytryptamine 2 (5-HT(2)) antiserotonergic activity and selectively binds with the 5-HT(2) receptor. The purpose of the present study is to assess the binding affinity and functional potency of naftidrofuryl to the 5-HT(2A) receptor, to find out the inverse agonist activity of this compound at a constitutively active mutant of 5-HT(2A) receptor, and finally to compare the findings with those of sarpogrelate. The investigation showed that the binding affinity (pK(i)) of naftidrofuryl was decreased 25- or 50-fold compared to sarpogrelate in the wild-type 5-HT(2A) receptor or Cys322Lys mutant receptor, respectively. Moreover, the functional potency (pK(b)) of naftidrofuryl was much lower compared to sarpogrelate at the 5-HT(2A) receptor. In addition, inverse agonist activity of naftidrofuryl was lower compared with sarpogrelate at the constitutively active mutant receptor. Thus, the data of the present study would be very important for the clarification of interaction sites of naftidrofuryl to 5-HT(2A) receptors and also may help to understand the mechanism of inverse agonist activity at the constitutively active mutant receptor.
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