Danysz W, Essmann U, Bresink I, Wilke R
Department of Pharmacology, Merz + Co., Frankfurt, Germany.
Pharmacol Biochem Behav. 1994 May;48(1):111-8. doi: 10.1016/0091-3057(94)90506-1.
Locomotor activity, ataxia, and stereotypy were assessed in the open field after administration of NMDA and AMPA antagonists acting by different mechanisms. The interaction with glutamatergic receptors was confirmed in the binding assay. (+)MK-801 and phencyclidine (PCP) produced similar changes in horizontal activity, i.e., a strong increase from the beginning of the test. Ketamine, and to a lesser extent, memantine, enhanced horizontal activity at the later observation periods only. Amantadine and NBQX produced a slight inhibition, while GYKI-52466, d-cycloserine, (+R)-HA-966, CGP-37849, and dextromethorphan were ineffective. Vertical activity (rearings) were inhibited by most agents except GYKI-52466 and gly-B partial agonists. At higher doses ataxia was seen after: MK-801, PCP, ketamine, memantine, amantadine, CGP-37849, dextromethorphan, and GYKI-52466. Hence, the inhibition of NMDA and AMPA receptors by agents acting at different recognition sites produces qualitatively different behavioral consequences.
在给予通过不同机制起作用的NMDA和AMPA拮抗剂后，在旷场中评估运动活性、共济失调和刻板行为。在结合试验中证实了与谷氨酸能受体的相互作用。（+）MK-801和苯环己哌啶（PCP）在水平活性上产生了类似的变化，即在试验开始时强烈增加。氯胺酮以及程度较轻的美金刚，仅在后期观察期增强了水平活性。金刚烷胺和NBQX产生了轻微抑制，而GYKI-52466、d-环丝氨酸、（+R）-HA-966、CGP-37849和右美沙芬无效。除了GYKI-52466和甘氨酸B部分激动剂外，大多数药物都抑制了垂直活性（直立）。在较高剂量下，在以下药物后出现共济失调：MK-801、PCP、氯胺酮、美金刚、金刚烷胺、CGP-37849、右美沙芬和GYKI-52466。因此，作用于不同识别位点的药物对NMDA和AMPA受体的抑制产生了质的不同行为后果。
