Affiliation:
1. Synthéval, 5 Rue Vaubénard, 14032 Caen Cedex, France
2. RLaboratoire de Pharmacologic UFR des Sciences Pharmacetiques, 1 Rue Vaubénard, 14032 Caen Cedex, France
3. Centre d'Etudes et de Recherche sur le Médicament de Normandie, Laboratoire de Pharmacochimie, UFR des Sciences Pharmaceutiques, 1 Rue Vaubénard, 14032 Caen Cedex, France
Abstract
Abstract
In the search for antipsychotic agents that are not associated with extrapyramidal side effects, efforts have been focused on finding selective D4-receptor antagonists and investigating their pharmacology. Our laboratory has developed a synthesis program for new pyrroloquinoxalines with therapeutic potential. We have described the synthesis of some new pyrroloquinoxalines with substituted arylpiperazino or aryltetrahydropyrido chain at position 3 of the quinoxaline ring (2-(4-phenylpiperazin-1-ylmethyl)-4-phenylpyr-rolo[1,2-a]quinoxalinium oxalate (3a), 2-[4-(2-methoxyphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3b), 2-[4-(3-trinuoromethylphenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[l,2-a]quinoxalinium oxalate (3c), 2-[4-(4-chlorophenyl)piperazin-1-ylmethyl]-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3d), 2-(4-pyridin-2-ylpiper-azin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3e), and 2-(4-phenyl-1,2,3,6-tetrahydropyridin-1-ylmethyl)-4-phenylpyrrolo[1,2-a]quinoxalinium oxalate (3f)).
A preliminary pharmacological study of these products was conducted using climbing behaviour induced by apomorphine (2.5 mg kg−1, s.c.) in mice. The derivatives were administered intraperitoneally 30 min before apomorphine. Haloperidol, chlorpromazine and clozapine were used as references.
Among this series, 3b, 3c and 3f revealed a central dopamine antagonist activity. The most active derivative was 3b, which exhibited a profile relatively close to clozapine.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
Cited by
34 articles.
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