Сертралин (золофт, стимулотон, асентра, серената, серлифт, торин, депрефолт, залокс, сертралофт, депралин, алевал, люстрал, мистрал)

Tatsumi et al. (1997) found Ki values of sertraline at the human SERT, DAT, and NET of 0.29, 25, and 420 nM, respectively.[98] The selectivity of sertraline for the SERT over the DAT was 86-fold.[98] In any case, of the wide assortment of antidepressants assessed in the study, sertraline showed the highest affinity of them all for the DAT, even higher than the norepinephrine–dopamine reuptake inhibitors (NDRIs) nomifensine (Ki = 56 nM) and bupropion (Ki = 520 nM).[98][109] Sertraline also has similar affinity for the DAT as the NDRI methylphenidate (Ki = 24 nM).[98][109] Tametraline (CP-24,441), a very close analogue of sertraline and the compound from which sertraline was originally derived, is an NDRI that was never marketed.[114]

Single doses of 50 to 200 mg sertraline have been found to result in peak plasma concentrations of 20 to 55 ng/mL (65–180 nM),[107] while chronic treatment with 200 mg/day sertraline, the maximum recommended dosage, has been found to result in maximal plasma levels of 118 to 166 ng/mL (385–542 nM).[6] However, sertraline is highly protein-bound in plasma, with a bound fraction of 98.5%.[6] Hence, only 1.5% is free and theoretically bioactive.[6] Based on this percentage, free concentrations of sertraline would be 2.49 ng/mL (8.13 nM) at the very most, which is only about one-third of the Ki value that Tatsumi et al. found with sertraline at the DAT.[98] A very high dosage of sertraline of 400 mg/day has been found to produce peak plasma concentrations of about 250 ng/mL (816 nM).[6] This can be estimated to result in a free concentration of 3.75 ng/mL (12.2 nM), which is still only about half of the Ki of sertraline for the DAT.[98]

As such, it seems unlikely that sertraline would produce much inhibition of dopamine reuptake even at clinically used dosages well in excess of the recommended maximum clinical dosage.[111] This is in accordance with its 86-fold selectivity for the SERT over the DAT according to Tatsumi et al. and hence the fact that nearly 100-fold higher levels of sertraline would be necessary to also inhibit dopamine reuptake.[111] In accordance, while sertraline has very low abuse potential and may even be aversive at clinical dosages,[115] a case report of sertraline abuse described dopaminergic-like effects such as euphoria, mental overactivity, and hallucinations only at a dosage 56 times the normal maximum and 224 times the normal minimum.[116] For these reasons, significant inhibition of dopamine reuptake by sertraline at clinical dosages is controversial, and occupation by sertraline of the DAT is thought by many experts to not be clinically relevant.