Biphalin—A Potent Opioid Agonist—As a Panacea for Opioid System-Dependent Pathophysiological Diseases?

Biphalin, one of the opioid agonists, is a dimeric analog of enkephalin with a high affinity for opioid receptors. Opioid receptors are widespread in the central nervous system and in peripheral neuronal and non-neuronal tissues. Hence, these receptors and their agonists, which play an important role in pain blocking, may also be involved in the regulation of other physiological functions. Biphalin was designed and synthesized in 1982 by Lipkowski as an analgesic peptide. Extensive further research in various laboratories on the antinociceptive effects of biphalin has shown its excellent properties. It has been demonstrated that biphalin exhibits an analgesic effect in acute, neuropathic, and chronic animal pain models, and is 1000 times more potent than morphine when administered intrathecally. In the course of the broad conducted research devoted primarily to the antinociceptive effect of this compound, it has been found that biphalin may also potentially participate in the regulation of other opioid system-dependent functions. Nearly 40 years of research on the properties of biphalin have shown that it may play a beneficial role as an antiviral, antiproliferative, anti-inflammatory, and neuroprotective agent, and may also affect many physiological functions. This integral review analyzes the literature on the multidirectional biological effects of biphalin and its potential in the treatment of many opioid system-dependent pathophysiological diseases.

Trp: a conserved aromatic residue crucial to the interaction of a scorpion peptide with sodium channels

Anti-tumour-analgesic peptide (AGAP), one scorpion toxin purified from Buthus martensii Karsch, was known as its analgesic and anti-tumour activities. Trp38, a conserved aromatic residue of AGAP, might play important roles in its interaction with sodium channels. In this study, a mutant W38F was generated and effects of W38F were examined on hNav1.4, hNav1.5 and hNav1.7 by using whole-cell patch-clamp, which were closely associated to the biotoxicity of skeletal and cardiac muscles and pain signalling. The data showed that W38F decreased the inhibition effects of peak currents of hNav1.7, hNav1.4 and hNav1.5 compared with AGAP, notably, W38F reduced the analgesic activity compared with AGAP. The results suggested that Trp38 be a crucial amino acid involved in the interaction with these three sodium channels. The decreased analgesic activity of W38F might result from its much less inhibition of hNav1.7. These findings provided more information about the relationship between structure and function of AGAP and may facilitate the modification of other scorpion toxins with pharmacological effects.

Clinical, behavioral and antinociceptive effects of crotalphine in horses

ABSTRACT: Crotalphine is a novel analgesic peptide that acts on kappa opioid and delta receptors, causing powerful analgesia in rats submitted to inflammatory, neuropathic or oncologic models of pain. This study evaluated clinical, behavioral and antinociceptive effects caused by crotalphine in horses, employing 18 Arabian horses and it was divided in three phases. In Phase I, "clinical and behavioral effects", crotalphine did not change the latency to urinate and defecate; did not modify the values of cardiac or respiratory rates, intestinal motility and rectal temperature; and did not cause significant ataxia, head, eye and lip ptosis. In Phase II, "antinociceptive effect on intact skin at scapular or ischial region", crotalphine did not cause significant analgesia. In Phase III, "antinociceptive effect on incised skin at scapular or ischial region", crotalphine promoted effective antinociceptive effects for six hours and inhibited hyperalgesia state for three days in the ischial region of horses submitted to incisional model of inflammatory pain, but crotalphine did not evoke relevant analgesic effect on the scapular region. Concluding, intravenous injection of a single dose of crotalphine (3.8ngkg-1) did not cause important clinical or behavioral changes and promotes antinociceptive effect on incised ischial region for seven days in horses. Moreover, crotalphine did not evoke relevant anti nociceptive effect on the scapular region or in intact skin of horses.