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

Abstract

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.

Analgesic Peptides: From Natural Diversity to Rational Design

“…Biphalin displays exceptionally high antinociceptive activity, induces analgesia in acute, neuropathic, and chronic animal pain models, and is 1000 times more potent than morphine when administered intrathecally. Moreover, in tests conducted on rodents after long-term administration, biphalin induces less physical dependence and withdrawal syndromes than morphine [150,151]. Despite its excellent antinociceptive activity, the clinical use of this compound is limited due to its poor penetration of the BBB and/or low metabolic stability.…”

The influence of a synthetic growth hormone‐releasing hormone analogue G11 and opioid peptide biphalin on selected fibroblasts parameters relevant to wound healing

“…The compound exhibits much greater analgesic potency and produces less side effects when compared with standard opioid analgesic, morphine. Furthermore, BIF was demonstrated to have many beneficial pleiotropic effects 28 . With respect to tissue regeneration, BIF was shown to improve epithelial (corneal) wound healing 29,30 and to accelerate wound closure in diabetic rats (i.a.…”

“…Furthermore, BIF was demonstrated to have many beneficial pleiotropic effects. 28 With respect to tissue regeneration, BIF was shown to improve epithelial (corneal) wound healing 29,30 and to accelerate wound closure in diabetic rats (i.a. by affecting the inflammatory phase).…”

Special Issue “Peptides for Health Benefits 2021”

“…In this review, the available findings on neuropeptide FF, cholecystokinin, melanocyte inhibitory factor, nociceptin/orphanin, ghrelin, oxytocin, endothelin, and venom peptides are described. The review by Redkiewicz et al [16] discusses in depth the data available after 40 years of research on the properties of biphalin, a dimeric analogue of enkephalin with a high affinity for opioid receptors. Its summarized analgesic, neuropathic, antipain, antiviral, antiproliferative, anti-inflammatory, and neuroprotective effects make this peptide a promising therapy for many opioid systemdependent pathological diseases.…”