Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: structure-activity studies.
Excitatory amino acid antagonists induce a phencyclidine-like catalepsy in pigeons: structure-activity studies.
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兴奋性氨基酸拮抗剂在鸽子中诱导苯环己哌啶样僵直症：结构活性研究。
DOI：
10.1016/0028-3908(87)90085-2
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发表时间：
1987
影响因子：
4.7
通讯作者：
Mudar,PJ
中科院分区：
文献类型：
--
作者：
Koek,W;Woods,JH;Mattson,MV;Jacobson,AE;Mudar,PJ
本文研究了兴奋性氨基酸拮抗剂L-2-氨基-5-磷酸戊酸(d，L-AP_5)及其异构体d-(−)-AP_5和l-(+)-AP_5，d，L-2-氨基-4-膦酸丁酸酯(AP_4)，d，L-2-氨基-7-磷酸庚酸、β-d-天冬氨酸氨甲基膦酸、顺式-2，3-哌啶二甲酸和γ-d-谷氨酸甲基磺酸在家鸽脑室内给药时产生环苯二胺(PCP)样反应的能力。尽管1-AP5和非选择性拮抗剂GAMS和cis-PDA都能产生毒性作用，但每种拮抗剂都能产生这种作用。产生过氧化氢酶的效价顺序为：AP7；D-AP5>；D，L-AP5>；顺式-PDA>；ASP-AMP>；AP4>；L-AP5>；GAMS；这些拮抗剂不能使家鸽脑内[~3H]N[1-(2-噻吩基)环己基]哌啶(苯环利定的同系物)从其识别部位移位。因此，由NMDA的兴奋性神经传递产生的PCP样过敏症-偏爱与PCP受体不同但相关的受体。这些结果有力地支持了这样一种假设，即利用NMDA受体，兴奋性突触的神经传递减少可能是PCP诱导的鸽子惊厥的基础。
The excitatory amino acid antagonistsd,l-2-amino-5-phosphonovalerate (d,l-AP5), its isomersd-(−)-AP5 andl-(+)-AP5,d,l-2-amino-4-phosphonobutyrate (AP4),d,l-2-amino-7-phosphonoheptanoate (AP7), β-d-aspartylaminomethylphosphonic acid (ASP-AMP),cis-2,3-piperidinedi-carboxylic acid (cis-PDA), and γ-d-glutamylaminomethylsulphonic acid (GAMS) were tested for their ability to produce a phencyclidine (PCP)-like catalepsy in pigeons when administered intracerebro-ventricularly. Each of the antagonists produced catalepsy, althoughl-AP5, and the non-selective antagonists GAMS andcis-PDA, produced the effect only at toxic doses. The rank order of potency to produce catalepsy was AP7 >d-AP5 >d,l-AP5 >cis-pda > ASP-AMP > AP4 >l-AP5 > GAMS; there was a strong positive correlation between this rank order of potencyvivoand the potency order of these compoundsin vitroas NMDA antagonists. The antagonists did not displace significant amounts of [3H]N[1-(2-thienyl)cyclohexyl]piperidine (a congener of phencyclidine) from its recognition site in the brain of pigeon. Thus, the PCP-like catalepsy that is produced by the excitatory neurotransmission at NMDA-preferring receptors that are distinct from, but related to, PCP receptors. The results strongly support the hypothesis that a reduction of neurotransmission at excitatory synapses, utilizing NMDA-preferring receptors, may underlie catalepsy in pigeons induced by PCP.