Comparative action of flunarizine, phenytoin, carbamazepine and two calcium‐entry blockers on spontaneous epileptiforrn bursts in the low calcium‐hippocampal slice preparation

Abstract

Ashton, D., K. Reid, R. Willems, R. Marrannes, and A. Wauquier: Comparative action of flunarizine, phenytoin, carbamazepine and two calcium-entry blockers on spontaneous epileptiform bursts in the low calcium-hippocampal slice preparation. Drug Dev. Res. a:397-405,1986 Exposure of hippocampal slices to a medium containing a low Ca2+-concentration and an increased concentration of Mg2+ and K+ resulted in the blockade of synaptic transmission and the development of spontaneous synchronized epileptiform bursts (SSEB) in area CA1. The SSEBs were measured extracellularly as a negative potential shift with superimposed population spikes. Flunarizine is a "Ca2+-entry blocker" with antiepileptic actions in humans. We compared flunarizine with two reference antiepileptics (phenytoin and carbamazepine) and two other "Ca2+-entry blockers" (verapamil and nimodipine) for their ability to reduce SSEBs. Flunarizine, which is insoluble in ACSF bathing medium, was applied in a nanodrop directly onto the CA1 region of the slice. All other drugs were applied in the bathing medium. changes in Ca2+ and K + did not occur before changes in potential, modulation of Ca2+ or K + channels in striatum pyrarnidale is unlikely to explain flunarizine's ability to reduce synchronized bursts. Further, the ability to block Ca2+ channels in the periphery appears to be unrelated to the ability to block SSEBs in this model. It is suggested that reduction of Na+ currents during depolarization may be the basis of the similar effects of phenytoin, carbamazepine and flunarizine in this model.

Palladium‐Catalyzed Chemoselective Allylic Substitution, Suzuki–Miyaura Cross‐Coupling, and Allene Formation of Bifunctional 2‐B(pin)‐Substituted Allylic Acetate Derivatives

“…Allylic amines are present in molecules with diverse pharmacological properties, such as Acrivastine (Semprex),45, 62 Flunarizine (Sibelium, Ca‐channel blocker),63, 64 and several γ‐aminobutyric acid (GABA) uptake inhibitors 65. In the synthesis of allylic amines, it is usually important that the geometry about the CC bond can be controlled to provide a single product.…”

Controlling Chemoselectivity in Vinyl and Allylic C−X Bond Activation with Palladium Catalysis: A pKa-Based Electronic Switch

“…To illustrate a practical application of this reversed reactivity, consider the approach we devised recently to prepare a molecular library of approximately 1400 allylic amines for biological evaluation (Scheme ) . Allylic amines are present as central motifs in molecules with diverse pharmacological properties such as Acrivastine (Semprex), Flunarizine (Sibelium, Ca channel blocker), and several GABA uptake inhibitors 5 …”

Stereoselective Vinylation of Aryl N-(2-Pyridylsulfonyl) Aldimines with 1-Alkenyl-1,1-heterobimetallic Reagents

“…Examples include Acrivastine (Semprex), 10 Flunarizine, 11 and several GABA uptake inhibitors. 12 As a result, additions to imines have attracted considerable attention.…”

“…Allylic amines are important pharmacophores that can exhibit significant biological properties. Examples include Acrivastine (Semprex), Flunarizine, and several GABA uptake inhibitors . As a result, additions to imines have attracted considerable attention.…”

“…It is noteworthy that 2-arylated trisubstituted ( E )-allylic amines are not currently accessible via the Tsuji–Trost reaction, because 2-arylated allylic acetates are not good substrates for the allylic substitution reaction . Given that amino ketones and allylic amines are important pharmacophores, − , we anticipate that the methods described herein will be useful to the synthetic community.…”