Quantitative autoradiography of [3H]indalpine binding sites in the rat brain: I. Pharmacological characterization.
The binding of [3H]indalpine (4-[2-(3-indolyl)]ethyl piperidine) to slide-mounted sections of rat brain has been characterized. This 5-hydroxytryptamine (5-HT) uptake blocker binds to sections with high affinity (KD approximately 1 nM). The binding is saturable, and can be displaced by the addition of clomipramine (1 microM). Other drugs inhibiting the uptake of 5-HT also have the capacity to inhibit the binding of [3H]indalpine. A significant correlation (r = 0.86) was found between the capacity of these compounds to inhibit the uptake of 5-HT and their potencies as inhibitors of [3H]indalpine binding. Binding was Na+ - and Cl- -dependent and was inhibited competitively by 5-HT. Furthermore, electrolytic lesions of the dorsal raphe or medial forebrain bundle, which cause a degeneration of 5-HT cell bodies and fibers, respectively, resulted in a 30-40% reduction in the binding of [3H]indalpine. [3H]Indalpine binds to the 5-HT uptake recognition sites in a different manner from imipramine-like compounds.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D007099:Imipramine / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism*; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D000928:Antidepressive Agents; D000929:Antidepressive Agents, Tricyclic; D010880:Piperidines; D012701:Serotonin; D007099:Imipramine; C018181:indalpine; D004298:Dopamine; D009638:Norepinephrine