Ensaculin (KA-672 HCl): a multitransmitter approach to dementia treatment.
Ensaculin, a novel benzopyranone substituted with a piperazine moiety, showed memory-enhancing effects in paradigms of passive and conditioned avoidance in both normal and artificially amnesic rodents. It exhibited neuroprotective activities in an NMDA toxicity model and neurotrophic effects in primary cultured rat brain cells. The compound could be characterized as a weak NMDA receptor-operated channel blocker. In receptor-binding studies, ensaculin was found to have high affinities to serotonergic 5-HT(1A) and 5-HT(7) receptors, adrenergic alpha(1), and dopaminergic D(2) and D(3) receptors. Due to its unique pharmacodynamic profile, ensaculin may have potential as an antidementia agent acting on various transmitter systems.
Clinical Research Department, Dr. Willmar Schwabe GmbH Co., Karlsruhe, Germany. robert.hoerr@schwabe.de.
Robert
R
Hoerr
Michael
M
Noeldner
D000818:Animals; D001578:Benzopyrans / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003704:Dementia / Q000188:drug therapy*; D006801:Humans; D008568:Memory / Q000187:drug effects; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D009435:Synaptic Transmission / Q000187:drug effects
D001578:Benzopyrans; C493593:DRD3 protein, human; D018696:Neuroprotective Agents; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D016194:Receptors, N-Methyl-D-Aspartate; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; C104425:serotonin 7 receptor; C112452:Ensaculin