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**ibudilast + riluzole** is a combination therapy under clinical investigation primarily for the treatment of amyotrophic lateral sclerosis (ALS). Ibudilast (also known as MN-166) is a small molecule inhibitor of phosphodiesterase-4 (PDE4), phosphodiesterase-10 (PDE10), and macrophage migration inhibitory factor (MIF); it is thought to reduce central nervous system (CNS) microglial activation, decrease pro-inflammatory cytokine secretion, and increase neurotrophic factors that support nerve cell survival. Riluzole is an approved ALS medication that modulates glutamatergic neurotransmission via inhibition of voltage-gated sodium channels, increased activation of glutamate reuptake, and possible postsynaptic potentiation of GABA_A receptors. This combination aims to slow disease progression and improve functional outcomes in ALS, with clinical trials suggesting additive or synergistic benefit compared to monotherapy—especially in early-stage ALS patients.
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