From ion channels to complex networks: magic bullet versus magic shotgun approaches to anticonvulsant pharmacotherapy.
Medical management and drug development for epilepsy emphasizes increasing pharmacological specificity to improve efficacy while minimizing side effects. However, growing evidence supports potential benefits of "magic shotgun" over "magic bullet" approaches to treatment of complex disease processes. We discuss experimental and theoretical evidence suggesting that seizures may be more amenable to a multi-target rather than a high-specificity approach, including evidence that individual anticonvulsants directly modulate a variety ion channel targets, the most direct determinants of neuronal excitability. Although the relevance of this promiscuity remains untested, it may contribute to anticonvulsant efficacy and should therefore be considered in drug development strategies and in therapeutic decision making.
Bianchi
Matt T
MT
Beth Israel Deaconess Medical Center, Sleep Medicine, 300 Brookline Ave, KS-4, Boston, MA 02115, United States. thebianchi@gmail.com
Pathmanathan
Jay
J
Cash
Sydney S
SS
D000927:Anticonvulsants / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D004827:Epilepsy / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects*; D007473:Ion Channels / Q000187:drug effects*; D008959:Models, Neurological; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D019338:Polypharmacy; D016896:Treatment Outcome
D000927:Anticonvulsants; D007473:Ion Channels