Allopurinol

Allopurinol is an old drug. Acting as a xanthine-oxidase inhibitor, it blocks purine degradation and has been safely used in the therapy of gout for many decades.

Infants with evolving hypoxic-ischemic encephalopathy may benefit from allopurinol because:

1. Following hypoxia-ischemia, allopurinol inhibits xanthine oxidase-mediated production of cytotoxic oxygen radicals during reperfusion. [reviews by Palmer Pediatr Res 1990, Warner, J Experiment Biol 2004, and Braunersreuther Curr Pharmaceut Biotechnol 2012]
2. Allopurinol seems to result in the accumulation of adenosine during hypoxia [Marro, Brain Research 2006], and adenosine is a potent inhibitory neuromodulator providing additional neuroprotection.
3. Allopurinol acts as an iron-chelator and direct scavenger of free radicals [Shadid, Neurosci Lett 1998].

Early clinical trials support the hypothesis that early postnatal allopurinol may improve outcome in infants with evolving hypoxic-ischemic encephalopathy. [vanBel, Paediatrics 1998, Benders, Arch Dis Child 2006, Gunes, Pediatr Neurol 2007]