Novel Benzo[b]quinolizinium Cations as Uncompetitive N-Methyl-D-aspartic Acid (NMDA) Antagonists: The Relationship between log D and Agonist Independent (Closed) NMDA Channel Block

A series of permanently charged benzo[b]quinolizinium cations having lower lipophilicity than MK-801 or phencyclidine (PCP) were synthesized. Data relating agonist independent block of N-methyl-D-aspartic acid (NMDA) ion channels to log D are described. Closed channel access is predicted to result i...

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Veröffentlicht in:Journal of medicinal chemistry 1995-09, Vol.38 (18), p.3586-3592
Hauptverfasser: Earley, William G, Kumar, Virendra, Mallamo, John P, Subramanyam, Chakrapani, Dority, John A, Miller, Matthew S, DeHaven-Hudkins, Diane L, Aimone, Lisa D, Kelly, Michael D, Ault, Brian
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Sprache:eng
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Zusammenfassung:A series of permanently charged benzo[b]quinolizinium cations having lower lipophilicity than MK-801 or phencyclidine (PCP) were synthesized. Data relating agonist independent block of N-methyl-D-aspartic acid (NMDA) ion channels to log D are described. Closed channel access is predicted to result in a more noncompetitive profile of antagonism compared to selective open channel blockers, which are uncompetitive inhibitors. Reduced closed channel block may underlie the absence of PCP or MK-801-like behavioral side effects observed for benzo[b]-quinolizinium cations.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00018a018