PHARMACOLOGICAL PROFILE OF ANTIDEPRESSANTS AND RELATED-COMPOUNDS AT HUMAN MONOAMINE TRANSPORTERS

Using radioligand binding assays, we determined the equilibrium dissoc iation constants (K-D's) for 37 antidepressants, three of their metabo lites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), s ome mood stabilizers, and assorted other compounds (some antiepileptic s, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihi stamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol w as the most potent at the human norepinephrine and dopamine transporte rs with K-D's of 0.45 +/- 0.03 nM and 8.1 +/- 0.4 nM, respectively. Se rtraline (K-D = 25 +/- 2 nM) and nomifensine (56 +/- 3 nM) were the tw o most potent antidepressants at the human dopamine transporter. We sh owed significant correlations for antidepressant affinities at binding to serotonin (R = 0.93), norepinephrine (R = 0.97), and dopamine (R = 0.87) transporters in comparison to their respective values for inhib iting uptake of monoamines into rat brain synaptosomes. These data are useful in predicting some possible adverse effects and drug-drug inte ractions of antidepressants and related compounds. (C) 1997 Elsevier S cience B.V.