title: Adaptations of NMDA and dopamine D2, but not of muscarinic receptors following 14 days administration of uncompetitive NMDA receptor antagonists.
abstract: Behavioral changes have previously been reported following administrations of uncompetitive NMDA receptor antagonists memantine, amantadine and MK-801 for 14 days, at the doses that produce plasma levels comparable to those seen in patients (20, 100 and 0.31 mg/kg/day respectively). Using the same doses, the effect on receptor binding (autoradiography) was studied in rats. [3H]MK-801 binding was increased in the dentate gyrus and CA3 region of the hippocampus (35.2 and 24.3% respectively) following 3 days S.C. infusion of memantine by ALZET minipumps. One daily injection of memantine for 14 days, increased [3H]MK-801 binding in the frontal cortex by 40.3%. The same treatment with amantadine did increase [3H]raclopride binding to dopamine D2 receptors by 13.5%. None of these treatments changed the expression of muscarinic receptors. It is concluded that subchronic blockade of the NMDA receptor by uncompetitive antagonists at moderate (therapeutically-relevant) doses induced only minor changes in NMDA and dopamine D2 receptor expression.
authors.affiliation: Department of Pharmacological Research, Merz + Co., Frankfurt/Main, Federal Republic of Germany.
authors.forename: M B
authors.initials: MB
authors.lastname: Hesselink
authors.forename: A G
authors.initials: AG
authors.lastname: De Boer
authors.forename: D D
authors.initials: DD
authors.lastname: Breimer
authors.forename: W
authors.initials: W
authors.lastname: Danysz
mesh_terms: D000547:Amantadine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002421:Caudate Nucleus / Q000502:physiology; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018728:Entorhinal Cortex / Q000502:physiology; D005625:Frontal Lobe / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D007263:Infusions, Parenteral; D007700:Kinetics; D008297:Male; D008559:Memantine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000502:physiology; D009928:Organ Specificity; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012457:Salicylamides / Q000493:pharmacokinetics; D013997:Time Factors
chemical_list: D017448:Receptors, Dopamine D2; D011976:Receptors, Muscarinic; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; D020891:Raclopride; D016291:Dizocilpine Maleate; D000547:Amantadine; D008559:Memantine