MK-801 AND MEMANTINE INHIBIT A CENTRALLY INDUCED INCREASE IN MYOCARDIAL OXYGEN-DEMAND IN RABBITS

Electrical stimulation of the paraventricular nucleus of the hypothala mus in the anaesthetized rabbit induces an increase in indexes of myoc ardial oxygen demand. This increase in myocardial oxygen demand is due to the activation of sympathetic pathways which include glutamatergic relays. In this model, systemic injection of dizolcipine (MK-801) and memantine inhibited these responses. Because these drugs have only on e pharmacological property in common i.e. blockade of the NMDA recepto r channel complex, these results fit with our previous results concern ing the possible involvement of NMDA receptors in the central control of sympathetic activation. Memantine appears to be an interesting prot otype for centrally acting cardioprotective drugs devoid of serious si de effects.