Behavioural and biochemical studies on 6-methylamino-4,5,6,7-tetrahydrobenzothiazole (14.839JL), a new potent dopaminergic agonist.
6-Methylamino-4,5,6,7-tetrahydrobenzothiazole monochlorhydrate (14.839JL) is a new, potent dopaminergic agonist. The stereotypy induced by this drug was greater than that induced by an equivalent dose of apomorphine, was antagonized by pretreatment with sulpiride and counteracted the hypomotility induced by reserpine. Striatal levels of the dopamine metabolites homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) were significantly lowered for up to 4-6 h by doses from 0.05 to 1 mg/kg. The drug was also very effective in lowering prolactine secretion. 14.839JL displaced [3H]N-n-propylnorapomorphine [3H]NPA from striatal binding sites with an IC50 similar to dopamine (DA). Conversely, the ability of 14.839JL to displace 3H spiperone from its binding sites was 100 and 10 times lower than that of haloperidol and sulpiride, and similar to that of SCH 23390. Differently from the latter, however, 14.839JL did not modify adenylate cyclase activity. All these data suggest that 14.839JL is a new, potent, long-lasting direct DA agonist, probably acting on D2 receptors.
Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
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Ponzio
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Algeri
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Garattini
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Cioce
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Rusconi
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Sacchetti
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Manuel
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Notelle
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Duvert
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Legeai
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011388:Prolactin / Q000097:blood; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*
D001679:Biogenic Amines; D011954:Receptors, Dopamine; D013844:Thiazoles; C054878:JL 14839; D013469:Sulpiride; D012110:Reserpine; D011388:Prolactin; D000262:Adenylyl Cyclases