Affinity and specificity of N-methyl- D-aspartate channel blockers affect their ability to disrupt prepulse inhibition of acoustic startle in rats.
Psychopharmacology February 1, 2003 Jenny L Wiley, Sarah A Harvey, Robert L Balster et al. 27 citations
Phencyclidine (PCP) and other high-affinity NMDA receptor channel blockers disrupt prepulse inhibition (PPI) of acoustic startle in rats, a model of sensorimotor gating relevant to attentional deficits in schizophrenia. This study tested NMDA channel blockers with varying affinities in Sprague-Dawley rats. High-affinity drugs dizocilpine and dextrorphan disrupted PPI at doses that did not alter startle responses alone. Low-affinity drugs showed mixed results: dextromethorphan and memantine disrupted PPI, while orphenadrine, amantadine, desipramine, and alaproclate did not. Ibogaine disrupted PPI only at doses that severely reduced startle. Not all NMDA channel blockers share PCP's PPI-disrupting effect, and caution is warranted for supratherapeutic doses and vulnerable populations.