Maj J, Rogóz Z, Skuza G, Jaros T
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1995 Jul-Aug;47(4):269-77.
CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline), two competitive AMPA (non-NMDA glutamate) receptor antagonists, as well as their interaction with CGP 37849, a competitive NMDA receptor antagonist, were studied in rats and mice. CNQX and NBQX inhibited the locomotor activity of naive rats. No symptoms of behavioral excitation were observed. CGP 37849 induced locomotor hyperactivity which was reduced by CNQX and NBQX. In monoamine-depleted rats (pretreated with reserpine + alpha-methyl-p-tyrosine), none of the two quinoxalines nor CGP 37849 antagonized akinesia. The antiakinetic effect of L-DOPA was increased by CGP 37849, but not by CNQX or NBQX. The latter action of CGP 37849 was decreased by CNQX and NBQX. The antiakinetic effect of clonidine was not changed by CNQX. The locomotor hyperactivity induced by apomorphine or cocaine was not modified by CNQX. Neither of the quinoxalines changed the catalepsy induced by haloperidol or spiperone. The fluphenazine catalepsy was slightly decreased by CNQX and increased by NBQX. CNQX and NBQX were inactive in the forced swimming test; CNQX (but not NBQX) increased the CGP 37849-induced reduction of the immobility time. CNQX decreased the muscle tone of hind limbs in naive and monoamine-depleted rats. The obtained results indicate that the AMPA receptor antagonists differ in their neuropharmacological profile from CGP 37849, an NMDA receptor antagonist. There is no positive cooperation (except for the forced swimming test) between NMDA and AMPA receptor antagonists; on the contrary, an antagonistic between them has been observed.
研究了两种竞争性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（非NMDA谷氨酸）受体拮抗剂CNQX（6-氰基-7-硝基喹喔啉-2,3-二酮）和NBQX（2,3-二羟基-6-硝基-7-氨磺酰基苯并[f]喹喔啉），以及它们与竞争性NMDA受体拮抗剂CGP 37849的相互作用。实验对象为大鼠和小鼠。CNQX和NBQX抑制了未用药大鼠的自发活动。未观察到行为兴奋症状。CGP 37849诱导自发活动亢进，而CNQX和NBQX可使其减弱。在单胺耗竭的大鼠（用利血平+α-甲基-对-酪氨酸预处理）中，两种喹喔啉和CGP 37849均不能对抗运动不能。CGP 37849可增强左旋多巴的抗运动不能作用，但CNQX或NBQX则无此作用。CNQX和NBQX可减弱CGP 37849的后一种作用。CNQX不改变可乐定的抗运动不能作用。CNQX不改变阿扑吗啡或可卡因诱导的自发活动亢进。两种喹喔啉均不改变氟哌啶醇或螺哌隆诱导的僵住症。CNQX可使氟奋乃静诱导的僵住症稍有减轻，而NBQX则使其加重。CNQX和NBQX在强迫游泳试验中无活性；CNQX（而非NBQX）增强了CGP 37849诱导的不动时间缩短。CNQX可降低未用药和单胺耗竭大鼠后肢的肌张力。所得结果表明，AMPA受体拮抗剂在神经药理学特征上与NMDA受体拮抗剂CGP 37849不同。NMDA和AMPA受体拮抗剂之间不存在正协同作用（强迫游泳试验除外）；相反，观察到它们之间存在拮抗作用。
