Direct Vascular Effects of Agents Used in the Pharmacotherapy of Cerebrovascular Disease on Isolated Cerebral Vessels

Abstract

Summary:The direct vasomotor effects of a number of agents used in the therapy of cerebral circulatory and metabolic disease were studied in isolated segments of cat pial vessels in vitro, Studies were repeated eight times gener ally, thus permitting the calculation of the mean maximum response-termed ifenprodil > vincamine > nicergoline > dihydroergotoxine > raubasine, In addition, it was considered worthwhile to determine whether the ifenprodil induced vasoconstriction occurred when human, rather than cat, pial vessels were studied, Ifenprodil and vincamine contracted the human vessels in a biphasic manner; the EC,;o was calculated to be 2,0 and 30 JLM, Based on the above observations, the following comments would appear justified, Firstly, an increase in cerebral blood flow does not necessarily mean a compound is a direct vasodilator. Secondly, the vasoconstrictory actions of some agents cor relate well with their anti-ischaemic properties (e,g" ifenprodil, vincamine, and nicergoline), Lastly, one action of effective anti-ischaemic agents might be to reduce flow, by vasoconstriction, in hyperaemic tissue: the inverse "steal" effect. Key Words: In vitro -a-adrenolytic agents-Middle cerebral artery Tension-Cat-Human.

Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI

“…F e Effect of TCN-201 pretreatment on CSD (no significant difference with corresponding control). studies on isolated cerebral vessels (Young et al, 1981). However, other in-vitro studies suggested the anti-vasoconstrictive effect of Ifenprodil (Arai et al, 1991) (McCool andLovinger, 1995).…”

Uncoupling DAPK1 from NMDA receptor GluN2B subunit exerts rapid antidepressant-like effects

“…Ifenprodil is an α1 adrenergic receptor antagonist that was originally developed as a vasodilator. 61 It was subsequently found to be a highly selective antagonist of the NMDA GluN2B subunit. 62 Upon ifenprodil binding, the bi-lobed structure of the GluN2 amino-terminal domain adopts a closed conformation, accompanied by rearrangement of the GluN1–GluN2 amino-terminal domain heterodimeric interface to inhibit receptor activity.…”

Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia

“…Ifenprodil has also been demonstrated to have some vasodilator effects via ␣-adrenoceptors, 9 and it is also known to constrict pial vessels. 48 These properties may result in an inverse steal phenomenon in which blood flow is diverted from the normal tissue toward the ischemic focus. 21 However, we did not observe any change in either mean ABP or CBF between saline-and ifenprodil-treated groups during ischemic and reperfusion periods.…”