Membrane action of tricyclic drugs. Spectroscopic studies of a series of phenothiazines compared with tricyclic antidepressive substances in red cell membrane, using the spin labelling technique.
Previous results were extended by binding studies of drugs on red cell membrane by means of the spin labelling technique. A series of phenothiazines was investigated and compared with several tricyclic antidepressive substances. It was found that phenothiazines at concentrations below 3 mumol/l decisively increase the order parameter of spin label 618, which reports on the interface of the membrane. Thus the fluidity of the interface is decreased. Spin label 616 reports on the hydrophobic membrane interior. Within this hydrophobic phase, the order is decreased by 100 mumol to 1 mmol/l of the phenothiazines. With tricyclic antidepressive substances, a rise of order parameter of spin label 618 is observed, which, however, is less steep. At about 30 mumol/l a maximum is eventually reached. At even higher concentrations of amitriptyline, nortriptyline or imipramine with spin label 616, however, no significant change of order parameter was observed indicating that perturbation of the hydrophobic membrane interior is not sensed. These findings thus corroborate our previous results, revealing that influence of phenothiazines can be measured through the polar and apolar phases of the membrane, while the antidepressive drugs primarily act on the polar phase.
D000929:Antidepressive Agents, Tricyclic / Q000097:blood / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D004910:Erythrocyte Membrane / Q000187:drug effects* / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010640:Phenothiazines / Q000097:blood / Q000494:pharmacology*; D012995:Solubility; D013113:Spin Labels
D000929:Antidepressive Agents, Tricyclic; D010640:Phenothiazines; D013113:Spin Labels; D006220:Haloperidol