Abstract |
Aniracetam is a therapeutically useful cognition enhancer for treating various neuropsychiatric symptoms occurring after cerebral infarction. We recently reported that local perfusion of its major metabolites N-anisoyl-GABA and p-anisic acid, but not aniracetam itself, enhanced acetylcholine (ACh) release with a delayed onset in cerebral regions of stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we examined the possible involvement of metabotropic and ionotropic glutamate (mGlu and AMPA) receptors in the N-anisoyl-GABA-induced ACh release using brain in vivo microdialysis. Basal ACh release in SHRSP was commonly lower in the nucleus reticularis thalami, dorsal hippocampus and prefrontal cortex than that in age-matched Wistar Kyoto rats. The delayed ACh release in the prefrontal cortex of SHRSP was completely blocked by MCPG, a group I and II mGlu receptor antagonist, and MCCG, a group II-selective mGlu receptor antagonist. In contrast, it was largely unaffected by AIDA, a group I-selective mGlu receptor antagonist, or by YM90K, an AMPA receptor antagonist. 1S,3R-ACPD, a preferential group II mGlu receptor agonist, enhanced ACh release with a similar latency and the effect was antagonized by MCCG, whereas AMPA induced a prompt ACh release. These results indicate that N-anisoyl-GABA and 1S,3R-ACPD share a common mechanism mediated by group II mGlu receptors in enhancing ACh release. The findings suggest a possible mechanism for aniracetam's clinical efficacy in stroke patients with cholinergic deficits.
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Authors | M Shirane, K Nakamura |
Journal | Neuropharmacology
(Neuropharmacology)
Vol. 39
Issue 5
Pg. 866-72
(Mar 03 2000)
ISSN: 0028-3908 [Print] England |
PMID | 10699452
(Publication Type: Journal Article)
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Chemical References |
- 1-aminoindan-1,5-dicarboxylic acid
- 2-methyl-2-(2-carboxycyclopropyl)glycine
- Amino Acids, Dicarboxylic
- Anisoles
- Benzoates
- Excitatory Amino Acid Antagonists
- Indans
- Quinoxalines
- Receptors, AMPA
- Receptors, Metabotropic Glutamate
- metabotropic glutamate receptor 2
- Cycloleucine
- 1-amino-1,3-dicarboxycyclopentane
- alpha-methyl-4-carboxyphenylglycine
- 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione
- N-anisoyl-GABA
- alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
- Acetylcholine
- Glycine
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Topics |
- Acetylcholine
(metabolism)
- Amino Acids, Dicarboxylic
(pharmacology)
- Animals
- Anisoles
(administration & dosage)
- Benzoates
(pharmacology)
- Cycloleucine
(administration & dosage, analogs & derivatives)
- Dose-Response Relationship, Drug
- Excitatory Amino Acid Antagonists
(pharmacology)
- Glycine
(analogs & derivatives, pharmacology)
- Hippocampus
(drug effects, metabolism)
- Indans
(pharmacology)
- Male
- Microdialysis
- Perfusion
- Prefrontal Cortex
(drug effects, metabolism)
- Quinoxalines
(pharmacology)
- Rats
- Rats, Inbred SHR
- Receptors, AMPA
(agonists, antagonists & inhibitors)
- Receptors, Metabotropic Glutamate
(agonists, antagonists & inhibitors, drug effects, metabolism)
- Thalamic Nuclei
(drug effects, metabolism)
- Wakefulness
- alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
(metabolism, pharmacology)
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