Ion Channel-Target Toxicology

The saying " use poison as an antidote to poison " has long been considered the spirit of traditional Chinese medicine and herbalism since Ming Dynasty and has indicated the medical values of toxins arising from venomous animals, plants, microbes, or synthetic chemicals. A well-known physician Sir P. M. Latham (1789–1875) once defined the relationship between poisons and medicines as " oftentimes the same substances given with different intents " , what highlighted the double-edged sword nature of toxins when applied with different doses. In view of the great potential of toxins as medicines and drug precursors, a stormy survey and pursuit has been implemented within pharmaceutical industry and research centers in a worldwide range. A classical example comes from the studies of a Brazilian scientist, Dr. Sergio Ferreira, who discovered, in the 1960s, bradykinin potentiating peptides (BPPs), extracted from the venom of the Brazilian viper Bothrops jararaca. These peptides were later shown to be able to decrease arterial pressure. This study was very important for the development of an analogue molecule, by Squibb Laboratory , called Captopril, one of the most successful examples of blockbuster drugs, used as an angiotensin converting enzyme inhibitor (ACEi), currently used in the treatment of hypertension, generating more than 8 billion dollars a year. Nowadays, a representative instance comes from the successfully commercialized toxin product " Ziconotide, " developed by Eli Lilly Incorporated (USA), from the venom of Conus. On the other side, JZMed Incorporated, a worldwide renowned market research firm specialized in the Chinese pharmaceutical industry, once forecasted that the Chinese preclinical and toxicology outsourcing industry would likely grow in a compound annual growth rate of 27% in five years after 2010 and its market value would likely reach more than $760 million by 2015. Despite the rapid growth and worldwide attention to toxin R&D industries, it has to be well recognized that the productivity of discovering a new medicine from toxins is still little efficient in the global biopharmaceutical industry. The hindrances toward toxin-drug transformation may include but not be limited to (1) overall costs of drug development ; (2) elimination of nondevelopable drug candidates; (3) extensive toxicology and safety pharmacology researches for any drug candidates. Among them, one of the major challenges of toxicity evaluation and integrated efficacy may be the targets of toxins in the human body. Up to now, it has been well documented that ion channels are specific …