The imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline is a dopamine-releasing agent in the rat striatum in vivo.
2-BFI (2-(2-benzofuranyl)-2-imidazoline) is a prototypical I2-imidazoline receptor ligand. In vivo, however, 2-BFI (1-20 mg/kg) decreased the synthesis of dopa/dopamine (DA) in rat striatum through mechanisms not related to interaction with I2-imidazoline receptors or to inhibition of the enzyme monoamine oxidase. The aim of this study was to unravel the mechanism underlying this potent effect of 2-BFI in brain. In vitro 2-BFI showed very low affinity for D2-dopamine receptors (K(i)=47 microM), and in vivo the drug (7 mg/kg) decreased the synthesis of striatal dopa/DA similarly in control rats (43%) and in rats pre-treated with alpha-methyl-para-tyrosine (50%) or cocaine (51%), indicating that this effect was not the result of D2-dopamine autoreceptor direct stimulation, inhibition of the enzyme tyrosine hydroxylase or blockade of neuronal DA reuptake. In DA-depleted (reserpine-treated) rats, however, 2-BFI did not inhibit significantly (11%), the synthesis of dopa/DA in the striatum, indicating that the effect of 2-BFI was indirectly mediated by endogenous DA through the activation of D2-dopamine autoreceptors. In conclusion, the I2-imidazoline receptor ligand 2-BFI is also a DA releasing agent in brain, and consequently a DA indirect agonist in vivo.
Laboratory of Neuropharmacology, Associate Unit of the Institute Cajal/CSIC, Department of Biology, University of the Balearic Islands, Cra. Valldemossa Km 7.5, E-07071, Palma de Mallorca, Spain.
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Sastre-Coll
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Esteban
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Miralles
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Zanetti
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García-Sevilla
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000345:Affinity Labels / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D054755:Imidazoline Receptors; D008297:Male; D020891:Raclopride / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects* / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D000345:Affinity Labels; D001572:Benzofurans; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D007093:Imidazoles; D054755:Imidazoline Receptors; D017448:Receptors, Dopamine D2; D011955:Receptors, Drug; D020891:Raclopride; C103723:2-(2-benzofuranyl)-2-imidazoline; D004298:Dopamine