**5.3.16 Ciclosporine A**

12 Amyotrophic Lateral Sclerosis

AVP-923 is a combinational formulation containing dextromethorphan hydrobromide, which is an NMDA antagonist and sigma-1 receptor agonist, and quinidine sulphate, which inhibits the cytochrome P450 2D6 (CYP2D6) enzyme. Dextromethorphan hydrobromide shows a high first pass metabolism in the liver, where it is metabolized by CYP2D6. Thus the addition of quinidine sulphate increases the bioavailability of dextromethorphan

AVP-923 was tested in two phase III trials in ALS patients with pseudobulbar affect (PBA), which is characterized by emotional dysregulation, such as uncontrollable outbursts of laughing or crying that are inappropriate to the emotions being experienced (Garnock-Jones, 2011; Olney & Rosen, 2010). The study showed that AVP-923 ameliorates symptoms of PBA in ALS patients and improved quality of life and quality of relationships (Brooks et al., 2004).

The immunosuppressant azathioprine in combination with prednisolone did not show a

The neuroprotective growth factor BDNF has been evaluated in a phase I/II clinical trial which reported a trend for prolonged survival after subcutaneous infusion (The BDNF Study Group & Bradley, 1995), a result which could not be reproduced in the subsequent phase III clinical trial (The BDNF Study Group (Phase III), 1999). The intrathecal

In clinical trials, branched chain amino acids did not show a beneficial effect in ALS patients

The dopamine agonist bromocriptine did not show a benefit in ALS patients (Szulc-

The anxiolytic agent buspirone did not show a benefit in ALS patients (The ALS

Ceftriaxone is a ß-lactam antibiotic which also shows anti-oxidant and anti-excitotoxity

Currently, ceftriaxone is evaluated in a phase III clinical trial in patients with ALS

Celecoxib is an inhibitor of cyclooxygenase-2 (COX-2), an enzyme which promotes inflammation by releasing of inflammatory substances, such as prostaglandin E(2) (PGE2).

**5.3.8 AVP-923 (Zenvia)** 

**5.3.9 Azathioprine** 

(Tandan et al., 1996).

**5.3.12 Bromocriptine** 

Kuberska et al., 1990).

**5.3.13 Buspirone** 

Association, 2010).

**5.3.14 Ceftriaxone** 

(NCT00349622).

**5.3.15 Celecoxib** 

effects (Traynor et al., 2006).

hydrobromide (Olney & Rosen, 2010).

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

**5.3.11 Branched-chain amino acids (BCAA)** 

**5.3.10 Brain-derived neurotrophic factor (BDNF)** 

administration was safe and well-tolerated (Ochs et al., 2000).

The branched-chain amino acids comprehend leucine, isoleucine, and valine.

The immunosuppressant cyclosporine A did not show a benefit in ALS patients (Appel et al., 1988).
