NMDA receptor affinities of 1,2-diphenylethylamine and 1-(1,2-diphenylethyl)piperidine enantiomers and of related compounds

We resolved 1,2-diphenylethylamine (DPEA) into its (S)- and (R)-enantiomer and used them as precursors for synthesis of (S)- and (R)-1-(1,2-diphenylethyl)piperidine, flexible homeomorphs of the NMDA channel blocker MK-801. We also describe the synthesis of the dicyclohexyl analogues of DPEA. These and related compounds were tested as inhibitors of [3H]MK-801 binding to rat brain membranes. Stereospecificity ranged between factors of 0.5 and 50. Some blockers exhibited stereospecific sensitivity to the modulator spermine. Our results may help to elucidate in more detail the NMDA channel pharmacophore.

Open-chain analogues of the prominent NMDA channel blocker MK-801 exhibit a high degree of stereoselectivity, inhibiting the binding of [3H]MK-801 to rat brain membranes (Ki).Figure optionsDownload as PowerPoint slide