Potentiation of anti-epileptic drugs effectiveness by pyronaridine in refractory epilepsy

Med Hypotheses. 2007;69(3):560-3. doi: 10.1016/j.mehy.2006.12.054. Epub 2007 Mar 26.


One of the major neurobiological mechanisms proposed in drug resistant epilepsy is removal of anti-epileptic drugs (AEDs) from the epileptogenic tissue through excessive expression of multi-drug efflux transporters such as P-glycoprotein (P-gp). P-gp, the encoded product of the human multi-drug resistance-1 (MDR-1; ABCB1) gene, is of particular clinical relevance in the emergence of multi-drug resistance (MDR), which may play an important role in preventing treatment response of some tumors and infectious diseases to chemotherapeutic agents and antibiotics. It has been shown that MDR-1 is over-expressed in brain tissue (hippocampal neurons) in patients with refractory temporal lobe epilepsy. For direct evidence that drug transporters such as P-gp are responsible for drug resistance, an experiment can be conducted to determine whether seizure control is improved when P-gp inhibitors are administered in addition to existing AEDs in patients with medically refractory epilepsy. In comparison with first and second-generation of P-gp inhibitors, third-generation inhibitors such as pyronaridine (PND) have advantages, such as higher potency and specificity for P-gp, lack of non-specific cytotoxicity, relatively long duration of action with reversibility, and good oral bioavailability. We suggest that a pilot study be conducted to determine whether adding of PND to existing AEDs decreases seizure frequency in patients with drug resistant epilepsy, and should this show promise, that a double-blind randomized controlled trial be designed to test the efficacy of PND.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / antagonists & inhibitors
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Drug Resistance
  • Drug Synergism*
  • Epilepsy / drug therapy*
  • Humans
  • Models, Biological
  • Models, Theoretical
  • Naphthyridines / pharmacology*
  • Treatment Outcome


  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anticonvulsants
  • Naphthyridines
  • pyronaridine