High- and low-affinity binding of [3H]imipramine in rat hypothalamus.
In the rat hypothalamus [3H]imipramine binding is inhibited by tricyclic and nontricyclic antidepressant drugs in a complex manner, with biphasic curves and Hill coefficients less than 1.0. 5-Hydroxytryptamine (serotonin) inhibited with high affinity a decreasing proportion of the [3H]imipramine binding sites as the [3H]imipramine concentration was raised. In the absence of sodium ions, IC50 values for the inhibition by tricyclic and nontricyclic antidepressants were increased by approximately 1,000-fold, and the inhibition curves became classically monophasic with Hill coefficients close to 1.0. These data are interpreted as suggesting that [3H]imipramine binds to two independent sites in the rat hypothalamus. One site is sodium-dependent with a high affinity for the drugs tested; the other is sodium-independent and has a low affinity for these drugs.
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D015283:Citalopram; D002997:Clomipramine / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D007099:Imipramine / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D000078764:Milnacipran; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology; D011437:Propylamines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology
D003521:Cyclopropanes; D010880:Piperidines; D011437:Propylamines; D015283:Citalopram; D000639:Amitriptyline; D012701:Serotonin; D017374:Paroxetine; D012964:Sodium; D000078764:Milnacipran; D002997:Clomipramine; D007099:Imipramine