Bethanidine (BW467C60) is a newly presented strong adrenergic neuron blocking factor which has a hypotensive operation in man. SENPs are essential for maintaining a balance between SUMOylation and deSUMOylation which can be disturbed by changing the expression of (sentrin-specific proteases) SENPs. SENP1 is the most studied isoform of SENPs. Hypertrophic stimuli can increase SENP1 expression using calcium/calcineurin-NFAT3 signaling in heart. Moreover, SENP1 expression may positively relate to the expression of mitochondrial genes of the heart, and can cause the heart and mitochondrial dysfunction.

MATERIALS AND METHODS:

In order to inhibit SENP1 using Bethanidine, molecular docking and molecular dynamics (MD) simulation of SENP1 with Bethanidine were performed. Molecular docking showed that Bethanidine can inhibit SENP1.

KEY FINDINGS:

MD Simulation showed that Bethanidine constitutes a stable complex with SENP1 as was evident from RMSD, RMSF, H-bond and DSSP plots. Free binding energy and the interaction patterns were obtained from molecular docking, and MD trajectory exhibited Bethanidine can be a potential drug candidate for SENP1 inhibition.

SIGNIFICANCE:

This study supplies enough evidences that Bethanidine is a potential inhibitor of SENP1 and can be applied for the treatment of cardiovascular diseases.

1994-11-01·European journal of pharmacology3区 · 医学

Tolerance to peripheral, but not central, effects of ropinirole, a selective dopamine D2-like receptor agonist

3区 · 医学

Article

作者: Pravin Raval ; Roger J. Eden ; Stephanie Yeulet ; Stephen G. Parker

Studies were conducted to determine possible development, and underlying mechanisms, of tolerance to the hypotensive effects of ropinirole (4-[2-(dipropylamino)ethyl]-1-3-dihydro-2H-indol-2-one HCl), a selective dopamine receptor agonist, following twice daily oral administration to cynomolgus monkeys and spontaneously hypertensive rats (SHR). Tolerance to the hypotensive effects of the compound developed in both species within one week of repeated dosing. Tolerance which developed in rats was dose-related and could not be attributed to altered plasma/drug concentrations or be overcome by increasing the i.v. challenge dose of ropinirole. Cross-tolerance was shown to the dopamine receptor agonist bromocriptine. Similar hypotensive responses to bethanidine were seen in rats treated with ropinirole or vehicle. Tolerance to hypolocomotor effects of the compound were not apparent in the same time frame. The dopamine D2 receptor antagonist, domperidone, caused hypertension in ropinirole-but not vehicle-treated rats. Results reported in this paper are not consistent with a down-regulation of peripheral dopamine D2-like receptors but suggest a compensatory increase in basal sympathetic tone.

100 项与 Bethanidine Sulfate 相关的药物交易

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