Drugs from Animal Venoms: Overcoming the Challenges to Treat Erectile Dysfunction

摘要

Animal venoms have a plethora of molecules (amines, salts, amino acids, proteins, and peptides, among others) and these venoms have been considered potential sources of new medicines. Examples of toxins from different animal venoms, which became therapeutic drugs, include captopril~R- an antihypertensive drug, based on a peptide template from the snake Bothrops jararaca's venom [1] and ziconotide or prialt~R, a peptide of 25 amino acid (aa) residues, derived from CONUS snail (Conus magus) [2] approved by the FDA in 2004 as an analgesic for the treatment of chronic pain. Also, exenatide (Byetta~R), a 39 aa residues, analogue of the glucagon-like peptide, derived from the saliva of the gila monster (Heloderma suspectum), has been used since 2005 for the treatment of type 2 diabetes [3]. The interest in the peptides derived from venoms has increased and is attested by several clinical trials or preclinical studies currently being developed [4]. Of note, accidents by certain arthropods such as scorpions and spiders can cause priapism, a painful, involuntary, and lasting erection. Noteworthy, this effect was observed in a victim, who was bitten by the "armed" spider Phoneutria nigriventer. The venom of this spider has several neurotoxins and most of them are peptides acting on ionic channels such as Na~+ and Ca~(2+) [5, 6]. Our group has studied a purified and extremely toxic peptide (LD50 = 0.7 μg/mouse) from this venom, called PnTx2-6 (also nominated δ-CNTX-Pn2a), which targets Na~+ channels and was previously shown to cause priapism in mice (for a review see [5, 7]). PnTx2-6 (0.1 nM), was able to potentiate erectile function in ex vivo preparation of Corpus cavernosum and in vivo anesthetized mice and rats, via nitric oxide (NO) [7, 8] a key mediator of penile erection.