**5.3.52 Nimodipine**

The calcium channel antagonist nimodipine showed no beneficial effect in a clinical trail in ALS patients (Miller et al., 1996).

### **5.3.53 NP001**

NP001 is a small molecule regulator of macrophage activation, which aims at restoring the neuroprotective state of macrophages, reducing inflammation, and normalizing the neuronal microenvironment.

NP001 has been tested in a phase I trial (NCT01091142) for safety and tolerability. It is currently evaluated in a subsequent phase II clinical trial (NCT01281631).

### **5.3.54 Olanzapine**

Olanzapine is an atypic neuroleptic drug used in psychiatry for the treatment of schizophrenia and other psychoses. One of its effects is also weight gain. In ALS patients, an involuntary weight loss of more than 10 percent of the original body weight correlates with an increased mortality. Thus treatment with olanzapine might increase the body weight, or, at least, keep it constant.

Currently, olanzapine is evaluated in a phase II/III study (NCT00876772) in ALS patients.

### **5.3.55 Olesoxime (TRO19622)**

Olesoxime is a neuroprotective agent with a cholesterol-like structure which is thought to act at the mitochondrial membrane (Bordet et al., 2010; Martin, 2010).

Currently, olesoxime is evaluated in a phase II/III trial (NCT00868166) as add-on to riluzole and a phase II/III safety extension study (NCT01285583).

### **5.3.56 Penicillamine**

The metal ion chelating agent penicillamine did not show a benefit in ALS patients (Conradi et al., 1982).

### **5.3.57 Pentoxifylline**

Pentoxifylline is an anti-apoptotic drug. It has been tested in a riluzole add-on phase II clinical trial, which did not show efficacy, but increased mortality (Meininger et al., 2006).
