The venoms from the cone snails are made up of a very diverse variety of toxins (conotoxins) which is divided into five major classes(α,δ,κ,μ,ω) depending on the target receptor. Among them, ω-Conotoxin –MVIIA (or Ziconitide) belongs to the ω-class and has very high affinity for the N-type calcium channels. For this reason MVIIA has been approved as a analgesics for severe and chronic pain by FDA approved in 2004. However, the severe side effects and administration mode of MVIIA make its adminisration restrictive. For example, MVIIA has been reported to have adverse effects associated with (i) nerve system caused by inhibiting N-type VSCCs of central nerve system and (ii) cardiovascular system caused by inhibiting autonomic nerve system to affect blood pressure and pulse rate.
Novel analgesic peptide, ω-conotoxin – FVIA can overcome problems associated with conventional ω-conotoxin, in particular, low specificity to N-type calcium channel and low reversibility. The FVIA peptide or its anlogues are an excellent analgesic drug candidate in the sense that they have a calcium channel blocking potency similar to MVIIA and a much less side effects than MVIIA. Furthermore, FVIA can be used as a pharmaceutical composition for preventing or treating diseases, disorders or conditions asscociated with N-type calcium channel activity.
ω-conotoxin – FVIA has the following features:
? Overcoming problems associated with low specificity to N-type calcium cannel and low reversibility
? Identifying the structures and functions of FIVA, thereby elucidating pivotal amino acid residues to reversibility of ω-conotoxin
? Preventing or treating for disease, disorder or condition which compring as following :
chronic pain conditions, acute pain, post-operative pain, mood disorders, anxiety disorders, depression, addiction disorders, gastrointestinal disorders, genitourinary disorders, neurotoxic injury associated with hypoxia , anoxia or ischemia , or schizophrenia
? Usage of the FVIA for manufacturing a medicament for preventing or treating disease, disorders or conditions associated with N-type calcium channel activity