**5.3.46 Memantine**

Memantine non-competitive antagonist at the NMDA and AMPA glutamate receptors with low affinity.

In two phase II/III clinical trials (NCT01020331, NCT00409721), memantine was safe and tolerated, but no efficacy has been found in ALS patients (de Carvalho et al., 2010).

### **5.3.47 Methylcobalamin (E0302, mecobalamin)**

Methylcobalamin is an analog of vitamin B12, which reduces the concentration of homocystein, an excitatory amino acid which showed toxic effects on motor neurons by inducing apoptosis.

ALS patients treated with high doses of methylcobalamin (MeCbl) showed an increase in compound muscle action potential amplitudes (CMAPs) after 4 weeks of treatment (Kaji et al., 1998). It increased the decline in ALS patients with regard to becoming respirator-bound (Izumi & Kaji, 2007).

Methylcobalamin is currently evaluated in two phase III studies (NCT00445172, NCT00444613) in ALS patients

### **5.3.48 Minocycline**

Minocycline has been described as anti-apoptotic and anti-inflammatory.

In a phase III study (NCT00047723), minocycline showed harmful effects of minocycline in ALS patients (Gordon et al., 2007).

### **5.3.49 Modafinil**

Modafinil is a psychostimulant clinically used for the treatment of narcolepsy and other sleep disorders.

Amyotrophic Lateral Sclerosis: An Introduction to Treatment and Trials 19

The inhibitor of cyclic adenosine monophosphate (cAMP) phosphodiesterase and cyclic guanine monophosphate (cGMP) phosphodiesterase phthalazinol did not show a benefit in

The acetylcholine esterase inhibitor physostigmine did not show a benefit in ALS patients

Pioglitazone activates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) (Gillies & Dunn, 2000; Kiaei, 2008). It has been used as anti-diabetic drug

In phase II clinical trial (NCT00690118), pioglitazone was found to be save and well-

In a riluzole add-on phase II study (NCT00919555), pioglitazone is currently evaluated in

The immunosuppressant prednisolone in combination with azathioprine did not show a

The anti-malaria drug pyrimethamine was found to reduce SOD1 levels in vitro and in vivo

Pyrimethamine is currently evaluated in a phase I/II trial (NCT01083667) for tolerability,

In two clinical trials, riluzole showed a moderate increase of about two months in survival after 21 and 18 months of treatment, respectively (Bensimon et al., 1994; Lacomblez et al., 1996). An open-label phase IV study (NCT00542412) found a longer survival in riluzole-

In subsequent population-based trials, older patients and patients with bulbar-onset had the biggest beneficial effect of riluzole, but the effects were transient and lost after longer

SB-509 is an engeineered zinc finger protein which up-regulates the transcription of the proangiogenic vascular entothelial growth factor A (VEGF-A) (Liu et al., 2001), which is also

Rasagiline is a monoamine oxidase type B inhibitor with neuroprotective effects. Rasagiline is currently evaluated in a phase II clinical trial (NCT01232738).

Riluzole is an anti-glutamatergic drug (Cheah et al., 2010; R.G. Miller et al., 2007).

periods of observation (Traynor et al., 2003; Zoccolella et al., 2007).

SB-509 is currently evaluated in a phase II clinical trial (NCT00748501).

neuroprotective and neuroregenerative (Maurer et al., 2008)

tolerated, but showed no effect on ALS disease progression (Ludolph et al., 2010).

**5.3.58 Phthalazine** 

**5.3.59 Physostigmine** 

(Norris et al., 1993).

**5.3.60 Pioglitazone** 

in diabetes type 2.

combination with tretinoin.

benefit in ALS patients (Werdelin et al., 1990).

in rodents as well as in humans (Lange, 2008).

safety, and efficacy in familial ALS.

treated patients of 92 days in median.

**5.3.61 Prednisolone** 

**5.3.62 Pyrimethamine** 

**5.3.63 Rasagiline** 

**5.3.64 Riluzole** 

**5.3.65 SB-509** 

ALS patients (Engel & Brooks, 1980).

It is currently evaluated in a phase IV study (NCT00614926) for the treatment of fatigue in ALS patients.

### **5.3.50 Naloxone**

The µ opioid receptor antagonist naloxone did not show a benefit in ALS patients (Silani et al., 1983).

### **5.3.51 Neostigmine**

The cholinesterase inhibitor did not show a benefit in ALS patients (Aquilonius et al., 1986).
