Relationships between chemical structure and inhibition of choline acetyltransferase by 2-(alpha-naphthoyl)ethyltrimethylammonium and related compounds.
Pharmacol Res Commun
; 20(9): 751-71, 1988 Sep.
Article
en En
| MEDLINE
| ID: mdl-3174803
A choline acetyltransferase (ChA) inhibitor with an optimum combination of properties of potency, stability and membrane permeability is required to study several functional aspects of acetylcholine in nervous and non-nervous tissues. Therefore, 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA), 2-(beta-naphthoyl)ethyltrimethylammonium iodide (beta-NETA), 2-(9'-anthroyl)ethyltrimethylammonium iodide (9'-AETA) and their corresponding tertiary dimethylamine hydrochloride analogs (alpha-NEDA, beta-NEDA, 9'-AEDA) were synthesized and tested for their ChA inhibitory activities. The quaternary ammonium compounds were more potent inhibitors (150 in microM: alpha-NETA, 9; beta-NETA, 76; 9'-AETA, 32) than the corresponding tertiary compounds (150 in microM: alpha-NEDA, 63; beta-NEDA, 1400; 9'-AEDA, 77). The alpha-naphthyl moiety was preferable to the beta-naphthyl- or 9'-anthryl moieties for alignment with the enzyme for inhibition. alpha-NETA and alpha-NEDA exhibited adequate ChA inhibitory potencies for further pharmacological studies and localization of membrane bound ChA. They exhibited fluorescent characteristics of the alpha-naphthyl moiety. Their ChA inhibition was not reversible by dialysis. They were considerably more potent for inhibiting ChA than cholinesterases and carnitine acetyltransferase.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Acetilcolina
/
Colina O-Acetiltransferasa
/
Compuestos de Amonio Cuaternario
/
Naftalenos
Límite:
Humans
Idioma:
En
Revista:
Pharmacol Res Commun
Año:
1988
Tipo del documento:
Article
Pais de publicación:
Estados Unidos