Dermorphin has been illegally used in horse racing as a performance-enhancing drug. Due to dermorphin's painkilling activity, horses treated with dermorphin may run harder than they would otherwise.
1. In 1980, the skin of certain frogs belonging to the genus Phyllomedusinae was found to contain two new peptides that proved to be selective mu-opioid agonists. Given the name dermorphins, these were the first members of a peptide family that in the past 15 years has grown to reach a total of seven naturally occurring peptides and nearly 30 synthetic analogs. 2. Dermorphin peptides are potent analgesics in rodents and primates, including man. Some dermorphins can enter the blood-brain barrier and produce central antinociception after peripheral administration. 3. The dermorphin family also includes mu 1-opioid receptor selective agonists that produce intense opioid analgesia, but stimulate pulmonary ventilation. 4. Experiments in rats and mice chronically exposed to dermorphins have shown that not only do they have higher antinociceptive efficacy and potency than morphine, but they are also less likely than morphine to produce tolerance, dependence and opiate side effects.
Dr. Rick Sams, director of the HFL Sport Science Lab in Lexington, Ky., said that when news of dermorphin first broke in 2012, he ordered several samples from commercial labs around the country to see what he was dealing with.
The version of dermorphin produced by frogs has a bonding structure that makes it dissolve rapidly in biological fluids before the substance has a chance to have an effect. An edit is needed to the bonding structure to make it hold together long enough to do its work. Initially, this caused a lot of confusion in testing laboratories, which had trouble pinpointing the structural difference.
Several of the samples Sams purchased, and the dermorphin detected in some of the first positive tests, were identical to the chemical structure of the dermorphin found in frogs. This meant that some of the first trainers who were caught using dermorphin were using a version that didn't work.
Because dermorphin's weight is so easily changed, Sams said that there hundreds, if not thousands, of possible variations (called analogues) of dermorphin. Figuring out which one to look for would take an incredibly lucky guess.
To further complicate matters, it's not difficult to have dermorphin, or any other amino acid, made. After the commercial success that stemmed from mass penicillin production toward the middle of the 20th century, a dramatic expansion of laboratories and pharmaceutical research began. Today, there are numerous labs across the world that require only a chemical diagram to make a given amount of an amino acid, and will do so for as little as a few hundred dollars.
Although Sams reports that he is looking into new testing technology for his lab that could one day make dermorphin analogue detection easier, he's quick to say that there are other substances found in animals that could be engineered similarly to dermorphin.
I guess some of the good news is that not many modifications of dermorphin result in compounds that have opiate activity. But all you need is one. You can't just willy-nilly make modifications and still have opiate activity for whatever reason.
Dermorphin is about 30-40 times more potent than morp but theoretically may be less likely to produce drug tolerance and addiction (due to its high potency). The amino acid sequence of dermorphin is H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2.Dermorphin is not found in humans or other mammals and similar D-amino acid peptides have only been found in bacteria, amphibians and molluscs. Dermorphin appears to be made in these through an unusual posttranslational modification carried out by an amino acid isomerase. This unusual process is needed because the D-alanine in this peptide is not among the 20 amino acids coded for in the genetic code and thus the peptide cannot be synthesized in the usual way from the encodings in the genome of an organism.
Last year, two quarterhorse trainers were suspended by the Louisiana State Racing Commission after stewards at Delta Downs suspended them for using the pain-killing drug dermorphin on horses. The stewards also disqualified the horses that tested positive and ordered purses won in the questioned races to be redistributed.
Traditionally the dried secretion of the skin was and is used by various tribes in countries around the Amazon (especially by the Katukina, Kaxinawá, Matsés, Mayoruna and Yawanawá people). These tribes applied or apply Sapo via the administration of cuts or burns in the skin during shamanistic hunting rituals. The application lead to enhanced hunting skills, partly due to the opioid analgesic activity of the compounds deltorphin, dermorphin and cerulein, probably all acting synergistically with each other, and with other bioactive peptides present in Sapo. These other peptides have broad mechanisms of actions, mainly on the level of the cardiovascular and the gastrointestinal system. Some of these peptides are phyllocaerulein, phyllokinin, sauvagine and adenoregulin.
Clearly, many of the bioactive peptides in Kambo are quite promising sources for modern medicine. Interesting painkilling molecules in Kambo are the opioid receptor agonist deltorphin, dermorphin and cerulein. None of these molecules are comparable to the structure of opioids, as they all are peptides (Table 1).
In the secretion of the frog at least 3 bioactive peptides have been isolated, with clear painkilling properties. Two of these peptides activate he morphine-related opioid receptor, MOR, and one has high affinity for the delta-opioid receptor, DOR. In animal models, all these 3 molecules have analgesic properties; dermorphin and cerulein have also been tested in humans, both in healthy volunteers, as well as in patients, for instance suffering from cancer pain.
Kambo is a very special mix of bioactive peptides. Its ritual use in the West since the beginning of our age is increasing. Users of Kambo report healing effects and sometimes explicite effects on symptoms, such as chronic pain. Kambo contains a great many interesting compounds, among which at least 3 peptides with painkilling activity. Especially dermorphin and cerulein might hold promise for future studies, since these peptides have already be tested for their efficacy and safety in patients. From the point of the anesthesiologist, the most suited indication would be intrathecal delivery of these two pepides in case of sever chronic cancer or postoperative pain.
Deltorphins and dermorphin are both powerful opioid receptor agonists. Deltorphins in particular have among the highest binding affinity and selectivity to delta opioid receptors of any natural compound. Dermorphin is highly selective for mu opioid receptors. Present at 5.2 and 0.25-0.33 micrograms per milligram, respectively, these peptides are many times more potent than endogenous beta-endorphin. 041b061a72