TY - JOUR
T1 - Pharmacological profile of antidepressants and related compounds at human monoamine transporters
AU - Tatsumi, Masahiko
AU - Groshan, Karen
AU - Blakely, Randy D.
AU - Richelson, Elliott
N1 - Funding Information:
This work is supported by Mayo Foundation for Medical Education and Research and USPHS grant MH27692 from N.I.M.H. We thank Dr. Zdenek B. Pristupa and Dr. H.B. Niznik, University of Toronto for supplying a cDNA encoding the human dopamine transporter.
PY - 1997/12/11
Y1 - 1997/12/11
N2 - Using radioligand binding assays, we determined the equilibrium dissociation constants (K(D)'s) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with K(D)'s of 0.45 ± 0.03 nM and 8.1 ± 0.4 nM, respectively. Sertraline (K(D) = 25 ± 2 nM) and nomifensine (56 ± 3 nM) were the two most potent antidepressants at the human dopamine transporter. We showed 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 inhibiting uptake of monoamines into rat brain synaptosomes. These data are useful in predicting some possible adverse effects and drug-drug interactions of antidepressants and related compounds.
AB - Using radioligand binding assays, we determined the equilibrium dissociation constants (K(D)'s) for 37 antidepressants, three of their metabolites (desmethylcitalopram, desmethylsertraline, and norfluoxetine), some mood stabilizers, and assorted other compounds (some antiepileptics, Ca2+ channel antagonists, benzodiazepines, psychostimulants, antihistamines, and monoamines) for the human serotonin, norepinephrine, and dopamine transporters. Among the compounds that we tested, mazindol was the most potent at the human norepinephrine and dopamine transporters with K(D)'s of 0.45 ± 0.03 nM and 8.1 ± 0.4 nM, respectively. Sertraline (K(D) = 25 ± 2 nM) and nomifensine (56 ± 3 nM) were the two most potent antidepressants at the human dopamine transporter. We showed 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 inhibiting uptake of monoamines into rat brain synaptosomes. These data are useful in predicting some possible adverse effects and drug-drug interactions of antidepressants and related compounds.
KW - 5-HT (5-hydroxytryptamine, serotonin) transporter, human
KW - Antidepressant
KW - Dopamine transporter, human
KW - Norepinephrine transporter, human
KW - Radioligand binding assay
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U2 - 10.1016/S0014-2999(97)01393-9
DO - 10.1016/S0014-2999(97)01393-9
M3 - Article
C2 - 9537821
AN - SCOPUS:0031565115
SN - 0014-2999
VL - 340
SP - 249
EP - 258
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -