Antagonistic effects of dipfluzine, flunarizine, and cinnarizine on 5-hydroxytryptamine-evoked contraction in pig basilar artery
Abstract
AIM: To investigate the effects of dipfluzine (Dip), a new derivative of cinnarizine (Cin), first developed by China, upon 5-hydroxytryptamine (5-HT)-induced contractions in cerebral arteries.
METHODS: Compared Dip, flunarizine (Flu), and Cin antagonistic effects and actions on 2-component contractions evoked by 5-HT in isolated pig basilar artery.
RESULTS: Dip showed a greater concentration-dependent antagonistic effect on 5-HT-evoked contraction than Cin and Flu in pig basilar artery rings. The order of potency (IC50) was Dip (4.0 mumol.L-1) > Flu (15.6 mumol.L-1) > Cin (25.2 mumol.L-1). All the Dip, Flu, and Cin inhibited 2-components of 5-HT-induced contraction. The antagonistic effects of Dip and Cin on the initial fast-phase contraction (FPC) were greater than that on the sustained tonic-phase contraction (STC), but Flu showed no difference between inhibiting effects on 2-component contractions.
CONCLUSION: Dip was more potent than both of Flu and Cin on cerebrovascular dilation, associated mainly with the inhibition of intracellular calcium release.
Keywords:
METHODS: Compared Dip, flunarizine (Flu), and Cin antagonistic effects and actions on 2-component contractions evoked by 5-HT in isolated pig basilar artery.
RESULTS: Dip showed a greater concentration-dependent antagonistic effect on 5-HT-evoked contraction than Cin and Flu in pig basilar artery rings. The order of potency (IC50) was Dip (4.0 mumol.L-1) > Flu (15.6 mumol.L-1) > Cin (25.2 mumol.L-1). All the Dip, Flu, and Cin inhibited 2-components of 5-HT-induced contraction. The antagonistic effects of Dip and Cin on the initial fast-phase contraction (FPC) were greater than that on the sustained tonic-phase contraction (STC), but Flu showed no difference between inhibiting effects on 2-component contractions.
CONCLUSION: Dip was more potent than both of Flu and Cin on cerebrovascular dilation, associated mainly with the inhibition of intracellular calcium release.