ISSN:
1432-2072
Keywords:
Key words NNC 19-1228
;
NNC 22-0031
;
Dopamine
;
Neuroleptic
;
Behavioral models
;
Rat
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract NNC 19-1228 [1-(3(6-benzothiazolylcarbamoyloxy)propyl)-4-(6-flouro-1,2-benzisoxazol-3-yl)piperidine] and NNC 22-0031 [4-(6-flouro-1,2-benzisoxazol-3-yl)-1-(3-(3,4-methylenedioxyphenylcarbamoyloxy)propyl)piperidine] are newly developed compounds with an in vitro pharmacologic profile similar to that of clozapine, i.e., mixed dopamine (DA), 5-hydroxytryptamine (5-HT)2 and α1-adrenergic antagonist action. In pharmacological experiments in mice, the compounds inhibited DA D2 receptor binding in vivo at doses that produced only moderate antagonism of methylphenidate (MPD)-induced stereotyped gnawing. However, the compounds were markedly more potent in blocking MPD-induced motility, a model which showed a high degree of sensitivity to α1-adrenergic antagonism, but not 5-HT2 antagonism. In rats, the NNC-compounds blocked conditioned avoidance responding and attenuated the discriminative stimulus effects of amphetamine, but failed to induce catalepsy. These results are discussed in terms of adrenergic, serotonergic and dopaminergic interactions which suggest that the NNC compounds may act as DA antagonists with mesolimbic selectivity, and thus may have efficacy as antipsychotics without coincident extrapyramidal side effects.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002130050177
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