Peripheral NMDA receptors may be involved in visceral nociceptive processing. As shown at SFN 2002 (#451.3), the brain impermeant, selective glycineB antagonist MRZ 2/596 was anti-allodynic in a rat model of irritable bowel syndrome (IBS) at 0.1 mg/kg i.p. Low brain penetration was confirmed in an in vitro model of the blood-brain barrier (BBB). MRZ 2/596 showed a permeability coefficient similar to the BBB-impermeant marker sucrose, 1.11 ± 0.05 x 10-5 (SD) cm/s and 0.77 ± 0.02 x 10-5 cm/s respectively. The in vitro data were consistent with brain microdialysis studies in awake rats, where MRZ 2/596 at the very high dose of 30 mg/kg i.p. generated maximal brain concentrations of only 0.11 uM. This compound at 25 mg/kg i.p was also completely inactive against maximal electroshock-induced convulsions (MES) in mice. The related moderately brain permeant compound MRZ 2/576 was also far more active in the IBS model than following systemic administration against MES or micro-iontophoretic excitation of single sp...