Inhibition of 5-HT uptake into neurons and platelets in mice treated chronically with chlorimipramine and femoxetine.
A single treatment with 5-HT uptake inhibitors potentiates the hypermotility in mice produced by the MAO-inhibitor nialamide. The effect of nialamide on motility was studied in mice after 4 weeks of feeding with a normal diet and diets containing various concentrations of the 5-HT uptake inhibitors chlorimipramine and femoxetine. Chronic treatment with the two substances enhanced the motor effects of nialamide about equally, which indicates a preservation of the neuronal 5-HT uptake inhibition during such treatment. The effect of chlorimipramine and femoxetine was obtained at plasma levels equivalent to or lower than the steady-state plasma concentrations found in patients treated with two 5-HT uptake inhibitors. Determination of decreased blood 5-HT after the 4 weeks of treatment was used as an in vivo test for inhibition of 5-HT uptake into platelets. Femoxetine was a much weaker depletor of blood 5-HT than chlorimipramine. These results indicate that blockade of neuronal 5-HT uptake is obtained at lower doses of femoxetine than blockade of 5-HT uptake into platelets. In contrast, chlorimipramine presumably inhibits 5-HT uptake into neurons and platelets at about the same dose.
D000818:Animals; D000840:Anisoles / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism*; D002997:Clomipramine / Q000097:blood / Q000494:pharmacology*; D003891:Desipramine / Q000097:blood; D005260:Female; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D009526:Nialamide / Q000494:pharmacology; D010880:Piperidines / Q000097:blood / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000097:blood / Q000494:pharmacology*; D013997:Time Factors
D000840:Anisoles; D010880:Piperidines; D012702:Serotonin Antagonists; D012701:Serotonin; C010655:femoxetine; D002997:Clomipramine; D009526:Nialamide; D003891:Desipramine