A novel class of Na+ and Ca2+ channel dual blockers with highly potent anti-ischemic effects.
A series of novel arylpiperidines (4a-d) which have highly potent blocking effects for both neuronal Na+ and T-type Ca2+ channels with extremely low affinity for dopamine D2 receptors were synthesized. Among these compounds, 1-(2-hydroxy-3-phenoxy)propyl-4-(4-phenoxyphenyl)-piperidine hydrochloride (4c; SUN N5030) exhibited remarkable neuroprotective activity in a transient middle cerebral artery occlusion (MCAO) model.
Annoura
H
H
Suntory Institute for Biomedical Research, Osaka, Japan.
Nakanishi
K
K
Uesugi
M
M
Fukunaga
A
A
Miyajima
A
A
Tamura-Horikawa
Y
Y
Tamura
S
S
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D020195:Epilepsy, Reflex / Q000517:prevention & control; D002546:Ischemic Attack, Transient / Q000517:prevention & control*; D051379:Mice; D008811:Mice, Inbred DBA; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D026941:Sodium Channel Blockers
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D018696:Neuroprotective Agents; D010647:Phenyl Ethers; D010880:Piperidines; C401940:SUN N5030; D026941:Sodium Channel Blockers