A novel series of mGluR2 positive allosteric modulators (PAMs), 1-[(1-methyl-1 H-imidazol-2- yl) methyl]-4-phenylpiperidines, is herein disclosed. Structure− activity relationship studies led to potent, selective mGluR2 PAMs with excellent pharmacokinetic profiles. A representative lead compound (+)-17e demonstrated dose-dependent inhibition of methamphetamine-induced hyperactivity and mescaline-induced scratching in mice, ...