Delaney AJ, Power JM, Sah P. Ifenprodil reduces excitatory synaptic transmission by blocking presynaptic P/Q type calcium channels. J Neurophysiol 107: 1571-1575, 2012. First published December 28, 2011; doi:10.1152/jn.01066.2011.-Ifenprodil is a selective blocker of NMDA receptors that are heterodimers composed of GluN1/GluN2B subunits. This pharmacological profile has been extensively used to test the role of GluN2B-containing NMDA receptors in learning and memory formation. However, ifenprodil has also been reported to have actions at a number of other receptors, including high voltage-activated calcium channels. Here we show that, in the basolateral amygdala, ifenprodil dose dependently blocks excitatory transmission to principal neurons by a presynaptic mechanism. This action of ifenprodil has an IC50 of similar to 10 mu M and is fully occluded by the P/Q type calcium channel blocker omega-agatoxin. We conclude that ifenprodil reduces synaptic transmission in the basolateral amygdala by partially blocking P-type voltage-dependent calcium channels.