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The role of excitatory amino acids in experimental models of Parkinson's disease

Summary

The aim of this article was to review the recent literature on the role of excitatory amino acids in Parkinson's disease and in animal equivalents of parkinsonian symptoms. Effects of NMDA and AMPA antagonists on the reserpine-induced akinesia, catalepsy and rigidity, on the neuroleptic-induced catalepsy, on the turning behaviour of 6-OHDA-lesioned rats, as well as on the parkinsonian symptoms evoked by MPTP in monkeys were analysed. Moreover, the role of NMDA antagonists in Parkinson's disease was discussed. Data concerning the protective influence of these drugs on degenerative properties of methamphetamine, MPTP and 6-OHDOPA were also presented. On the basis of the above findings, the following conclusions may be drawn: (1) disturbances in the glutamatergic transmission in various brain structures seem to play a significant role in the development of symptoms o Parkinson's disease; (2) the NMDA-receptor blocking component may make a substantial contribution to the therapeutic effect of antiparkinsonian drugs; a similar contribution of AMPA-receptor blocking component has not been sufficiently documented, so far; (3) compounds blocking NMDA receptors may possibly prevent the development of Parkinson's disease; this presumption needs, however further studies; (4) side effects of NMDA receptor antagonists may be a limiting factor in the use of these compounds in humans.

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Abbreviations

trans ACPD:

trans-1-amino-cyclopentane-1, 3 dicarboxylic acid

αMT:

α-methyl-p-tyrosine

AMPA:

α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate

L-AP4:

2-amino-4-phosphonobutyric acid

AP5:

DL-2-amino-5-phosphonovaleric acid

AP7:

2-amino-7-phosphonoheptamoic acid

budipine:

1-t-butyl-4, 4-diphenylpiperidine

L-BMAA:

β-N-methylamino-l-alanine

CGP 37849:

(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid

CGP 39551:

(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid ethylester

CGS 19755:

cis-4-phosphonomethyl-2-piperidine-carboxylic acid

CNQX:

6-cyano-7-nitroquinozaline-2, 3-dione

CPP:

3-(2-carboxy-piperazine-4-yl)-propyl-1-phosphonic acid

CPPene:

(E)-4-(3-phosphonoprop-2-enyl)-piperazine-2-carboxylic acid

CY 208-243:

(−)-4,6,6a,7,8,12b-hexahydro-7-methyl-indolo[4,3a-b]phenanthyxidine

DOPAC:

3,4-dihydroxyphenylacetic acid

GDEE:

L-glutamic acid diethylester

HVA:

homovanillic acid

lamotrigine:

3,5-diamino-6-[2,3-dichlorophenyl]-1,2,4-triazine

L-DOPA:

3,4-dihydroxyphenyl-L-alanine

MAO:

monoamine oxidase

MK-801:

dizocilpine

MPDP+ :

1-methyl-4-phenyldihydropyridinium

MPP+ :

1-methyl-4-phenyl-pyridinium

MPTP:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

NBQX:

6-nitro-7-sulfamobenzo(f)quinoxaline-2,3-dione

NMDA:

N-methyl-D-aspartate

NPC 26126:

2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid

6-OHDA:

6-hydroxydopamine

6-OHDOPA:

6-hydroxydopa-2,4,5-trihydroxyphenylalanine

PCP:

phencyclidine

(+)-PHNO:

(+)-4-propyl-9-hydroxynaphthoxazine

SL 82.0715:

(±) α-(4-chlorophenyl)-4-[(4-fluorophenyl) methyl]-1-piperidineethanol

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Ossowska, K. The role of excitatory amino acids in experimental models of Parkinson's disease. J Neural Transm Gen Sect 8, 39–71 (1994). https://doi.org/10.1007/BF02250917

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Keywords

  • Parkinson's disease
  • animal models
  • NMDA
  • antagonists
  • AMPA antagonists
  • therapy
  • neuroprotection