Table 1.
Summary of pharmacologic properties
| Chemical structure | (S)-(+)-2-[4-(3-fluorobenzyl) oxybenzyl) aminopropanamide methanesulfonate (see Figure 1), water stable, small molecule |
|---|---|
| Drug name | Xadago®, safinamide (generic) |
| Phase | IV, approved in 2015 in the EU |
| Indication | Fluctuating levodopa-treated patients with Parkinson’s disease |
| Mechanism of action | Reversible inhibition of MAO-B, inhibition of abnormal glutamate release, modulation of NA+- and Ca++ channels |
| Administration route | Oral |
| Dosing | 50 or 100 mg once in 1 day |
| Pivotal trials in levodopa-treated PD patients | SETTLE Study:42; 016 Study,40 018 study extension41 |
| Absorption | Gastrointestinal |
| Inhibition of dopamine uptake (human; CHO-K1 cells) | IC50 =8.44 μM |
| Blocking of dopamine transporter sites (human; CHO-K1 cells) | 50% at 10 μM |
| Dopamine (rat brain) | IC50 =12 μM |
| Serotonine (rat brain) | IC50 =21 μM |
| Interaction with dopamine transporter (rat brain) | IC50 =9 μM |
| Interaction with serotonine transporter (rat brain) | IC50 =6 μM |
| MAO-B (rat brain) | IC50 =0.098 μM |
| MAO-A (rat brain) | IC50 =485 μM |
| MAO-B (human brain) | IC50 =0.079 μM |
| MAO-A (human brain) | IC50 =80 μM |
| Blocking of veratridine-induced glutamate release (rat) | IC50 =56 μM |
| Blocking of K+-induced glutamate release (rat) | IC50 =9 μM |
| Interval to maximum concentration | 2–4 hours |
| Bioavailability | 95% |
| Plasma protein binding | 88%–90% |
| Terminal half-life | 22 hours (range: 22–30) |
| Elimination | Hepatic |
Abbreviations: IC50, half-maximal inhibitory concentration; EU, European Union; MAO, monoamine oxidase.