Syntheses and pharmacological evaluations of novel N-substituted bicyclo-heptane-2-amines at N-methyl-D-aspartate receptors.

Several novel norcamphor (bicycloheptane)-based compounds were designed and synthesized as non-competitive N-methyl-D-aspartate receptor antagonists at the phencyclidine binding sites. The heterocyclic ring was also varied to examine piperidine, pyrrolidine, and morpholine groups. We examined pharmacological activities of these compounds in vitro (binding studies) and in vivo (maximal electroshock test). Pharmacological evaluations revealed one of the compounds, 5a, to be a good lead, exhibiting moderate binding at N-methyl-D-aspartate receptors (IC(50) =7.86 μm; K(i) =5.28 μm), maximal electroshock neuroprotection activity at 100 mg/kg and acceptable toxicity profile.