The co-agonism between glutamate and glycine at the NMDA receptor raises uncertainty about the estimation of the values of dissociation constants for agonists and antagonists and of efficacy for agonists. In this article, Mauro Corsi, Paolo Fina and David Trist discuss how to analyse the interaction of the two agonists with the NMDA receptor by applying an operational receptor model. Data simulation indicates that co-agonism can affect the potency as well as the efficacy of agonists. Moreover, the interaction of antagonists with the NMDA receptor can also be affected, leading to altered estimation of the antagonist dissociation constants.