Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate
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-HT2) antiserotonergic activity and selectively binds with the 5-HT2 receptor. The purpose of the present study is to assess t...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2009-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131931151X |
| _version_ | 1828413640365047808 |
|---|---|
| author | Saida Abdel Regal Aly Murad Hossain Mohiuddin Ahmed Bhuiyan Takashi Nakamura Takafumi Nagatomo |
| author_facet | Saida Abdel Regal Aly Murad Hossain Mohiuddin Ahmed Bhuiyan Takashi Nakamura Takafumi Nagatomo |
| author_sort | Saida Abdel Regal Aly |
| collection | DOAJ |
| description | 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-HT2) antiserotonergic activity and selectively binds with the 5-HT2 receptor. The purpose of the present study is to assess the binding affinity and functional potency of naftidrofuryl to the 5-HT2A receptor, to find out the inverse agonist activity of this compound at a constitutively active mutant of 5-HT2A receptor, and finally to compare the findings with those of sarpogrelate. The investigation showed that the binding affinity (pKi) of naftidrofuryl was decreased 25- or 50-fold compared to sarpogrelate in the wild-type 5-HT2A receptor or Cys322Lys mutant receptor, respectively. Moreover, the functional potency (pKb) of naftidrofuryl was much lower compared to sarpogrelate at the 5-HT2A 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-HT2A receptors and also may help to understand the mechanism of inverse agonist activity at the constitutively active mutant receptor. Keywords:: naftidrofuryl, inverse agonist activity, constitutively active mutant, sarpogrelate |
| first_indexed | 2024-12-10T13:12:32Z |
| format | Article |
| id | doaj.art-f472e63f0f6c46c7be0d6b6cc29ed535 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-10T13:12:32Z |
| publishDate | 2009-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-f472e63f0f6c46c7be0d6b6cc29ed5352022-12-22T01:47:38ZengElsevierJournal of Pharmacological Sciences1347-86132009-01-011104445450Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of SarpogrelateSaida Abdel Regal Aly0Murad Hossain1Mohiuddin Ahmed Bhuiyan2Takashi Nakamura3Takafumi Nagatomo4Department of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan; Corresponding author. nagatomot@s4.dion.ne.jpAbstract.: Naftidrofuryl is a peripheral vasodilator that has been clinically used in the treatment of intermittent claudication and dementia. It has 5-hydroxytryptamine 2 (5-HT2) antiserotonergic activity and selectively binds with the 5-HT2 receptor. The purpose of the present study is to assess the binding affinity and functional potency of naftidrofuryl to the 5-HT2A receptor, to find out the inverse agonist activity of this compound at a constitutively active mutant of 5-HT2A receptor, and finally to compare the findings with those of sarpogrelate. The investigation showed that the binding affinity (pKi) of naftidrofuryl was decreased 25- or 50-fold compared to sarpogrelate in the wild-type 5-HT2A receptor or Cys322Lys mutant receptor, respectively. Moreover, the functional potency (pKb) of naftidrofuryl was much lower compared to sarpogrelate at the 5-HT2A 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-HT2A receptors and also may help to understand the mechanism of inverse agonist activity at the constitutively active mutant receptor. Keywords:: naftidrofuryl, inverse agonist activity, constitutively active mutant, sarpogrelatehttp://www.sciencedirect.com/science/article/pii/S134786131931151X |
| spellingShingle | Saida Abdel Regal Aly Murad Hossain Mohiuddin Ahmed Bhuiyan Takashi Nakamura Takafumi Nagatomo Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate Journal of Pharmacological Sciences |
| title | Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate |
| title_full | Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate |
| title_fullStr | Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate |
| title_full_unstemmed | Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate |
| title_short | Assessment of Binding Affinity to 5-Hydroxytryptamine 2A (5-HT2A) Receptor and Inverse Agonist Activity of Naftidrofuryl: Comparison With Those of Sarpogrelate |
| title_sort | assessment of binding affinity to 5 hydroxytryptamine 2a 5 ht2a receptor and inverse agonist activity of naftidrofuryl comparison with those of sarpogrelate |
| url | http://www.sciencedirect.com/science/article/pii/S134786131931151X |
| work_keys_str_mv | AT saidaabdelregalaly assessmentofbindingaffinityto5hydroxytryptamine2a5ht2areceptorandinverseagonistactivityofnaftidrofurylcomparisonwiththoseofsarpogrelate AT muradhossain assessmentofbindingaffinityto5hydroxytryptamine2a5ht2areceptorandinverseagonistactivityofnaftidrofurylcomparisonwiththoseofsarpogrelate AT mohiuddinahmedbhuiyan assessmentofbindingaffinityto5hydroxytryptamine2a5ht2areceptorandinverseagonistactivityofnaftidrofurylcomparisonwiththoseofsarpogrelate AT takashinakamura assessmentofbindingaffinityto5hydroxytryptamine2a5ht2areceptorandinverseagonistactivityofnaftidrofurylcomparisonwiththoseofsarpogrelate AT takafuminagatomo assessmentofbindingaffinityto5hydroxytryptamine2a5ht2areceptorandinverseagonistactivityofnaftidrofurylcomparisonwiththoseofsarpogrelate |