Indorenate modifies a1-adrenergic and benzodiazepine receptor binding in the rat brain: an autoradiography study.
Indorenate (5-methoxytryptamine-beta-methylcarboxylate) is a 5-HT1A receptor agonist that produces antihypertensive, anxiolytic, antidepressant and anticonvulsant effects. However, there is evidence suggesting that these effects could involve the activation of benzodiazepine (BZD) receptors but not the activation of a1-adrenergic receptors. The goal of this study was to analyse the effect of indorenate on a1-adrenergic and BZD receptor binding in specific rat brain areas by using in-vitro autoradiography. Coronal brain sections from male Wistar rats were used for labelling 5-HT1A (3H-8-OH-DPAT, 2 nM), a1-adrenergic (3H-prazosin, 2 nM) and BZD (3H-flunitrazepam, 2 nM) receptor binding in the presence or absence of indorenate (1 microM). Indorenate totally displaced 3H-8-OH-DPAT binding in all the brain areas evaluated. It decreased 3H-prazosin binding just in the frontal (30%) and sensorimotor (32%) cortices and in the thalamus (21%). Additionally, indorenate diminished 3H-flunitrazepam binding only in the cingulate (16%) and piriform (18%) cortices as well as in the dorsal raphe nucleus (18%). These results confirm that indorenate is a 5-HT1A ligand and suggest the possible participation of a1-adrenergic and BZD receptors in its pharmacological properties.
López-Meraz
M L
ML
Department of Neurology, David Geffen School of Medicine at UCLA, and Epilepsy Research Laboratory, VA Greater Los Angeles Healthcare System, West Los Angeles, CA 90073, USA. lopezmerazml@ucla.edu
Neri-Bazán
L
L
Rocha
L
L
D008735:5-Methoxytryptamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000378:metabolism; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism* / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D014151:Anti-Anxiety Agents; D018491:Dopamine Agonists; D018340:Receptors, Adrenergic, alpha-1; D011963:Receptors, GABA-A; D044282:Receptor, Serotonin, 5-HT1A; D008735:5-Methoxytryptamine; D005445:Flunitrazepam; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C033600:indorenate; D011224:Prazosin