Stimulatory effects of clonidine,cirazoline and rilmenidine on locus coeruleus noradrenergic neurones: possible involvement of imidazoline-preferring receptors |
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Authors: | Joseba Pineda Luisa Ugedo Jesús A. García-Sevilla |
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Affiliation: | (1) Department of Pharmacology, Medical School, University of the Basque Country, E-48940 Leioa, Bizkaia, Spain;(2) Laboratori de Neurofarmacologia, Deparament de Biologia Fonamental i Ciències de la Salut, Universitat de les Illes Balears, Cra Valldemossa Km 7.5, E-07071 Palma de Mallorca, Spain |
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Abstract: | Summary Clonidine and related drugs not only interact with 2-adrenoceptors but also recognise non-adrenoceptor sites in the brain. The involvement of these imidazoline-preferring receptors in the regulation of the activity of locus coeruleus noradrenergic neurones (NA-LC) was investigated after inactivation of 2-adrenoceptors with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). In EEDQ-pretreated rats (6 mg/kg, i.p., 6 h), the characteristic inhibitory effect of low doses of clonidine on these neurones was abolished and a paradoxical, dose-dependent increase in firing rate was observed at higher doses (640–5120 g/kg, i.v.) (ED50 = 702 g/kg, Emax = 83 %, n = 14). Guanfacine (0.3–20 mg/kg) did not modify neuronal activity but antagonised the stimulatory effect of clonidine. Cirazoline (80–640 g/kg) and rilmenidine (0.3–10 mg/kg) also stimulatedneuronal activity(ED50 = 192 g/kg, Emax = 102%, n = 5; ED50 = 1563 g/kg, Emax = 70%, n = 1–5, respectively) by an 2-adrenoceptor-independent mechanism. The results suggest that these drugs can modulate the activity of locus coeruleus noradrenergic neurones through the activation of I1-imidazoline-preferring receptors. |
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Keywords: | Clonidine Cirazoline Rilmenidine Imidazoline-preferring receptors Locus coeruleus noradrenergic neurones |
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