MK-801 and memantine inhibit a centrally induced increase in myocardial oxygen demand in rabbits.
Electrical stimulation of the paraventricular nucleus of the hypothalamus in the anaesthetized rabbit induces an increase in indexes of myocardial 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 one pharmacological property in common i.e. blockade of the NMDA receptor channel complex, these results fit with our previous results concerning the possible involvement of NMDA receptors in the central control of sympathetic activation. Memantine appears to be an interesting prototype for centrally acting cardioprotective drugs devoid of serious side effects.
Monassier
L
L
Laboratoire de Pharmacologie Cardiovasculaire et Rénale, CNRS ERS 109, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
Tibiriça
E
E
Roegel
J C
JC
Feldman
J
J
Bousquet
P
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000502:physiology; D011817:Rabbits; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008559:Memantine