GABA uptake inhibitors produce a greater antinociceptive response in the mouse tail-immersion assay than other types of GABAergic drugs.
Life Sci
; 37(20): 1901-12, 1985 Nov 18.
Article
en En
| MEDLINE
| ID: mdl-4058259
ABSTRACT
Antinociception produced by the GABA uptake inhibitors d,l- SKF-89976A and SKF-100330A was characterized and compared to that produced by other types of GABAergic drugs. Using the mouse tail-immersion assay it was found that the antinociception produced by the uptake inhibitors was antagonized by scopolamine, a cholinergic muscarinic receptor antagonist. However, neither SKF compound demonstrated any significant affinity for muscarinic receptor binding sites suggesting that they are not direct-acting cholinomimetics. In vitro uptake experiments revealed that the SKF compounds selectively inhibit GABA transport, having no effect on the accumulation of aspartic acid, glutamic acid, beta-alanine or glycine. Moreover, antinociception and GABA uptake inhibition were stereoselective for SKF-89976A, with the d-isomer being more active in both tests. When comparing antinociceptive responses at maximally effective doses it was also found that the SKF compounds were substantially more efficacious than direct-acting GABA receptor agonists or a GABA transaminase inhibitor. These data suggest that uptake inhibitors may be facilitating GABA transmission in a system that is less affected by other types of GABAergic compounds.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Dolor
/
Encéfalo
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Antagonistas del GABA
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Analgésicos
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Ácidos Nicotínicos
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Ácidos Nipecóticos
Límite:
Animals
Idioma:
En
Revista:
Life Sci
Año:
1985
Tipo del documento:
Article