Analgesic activity of a novel bivalent opioid peptide compared to morphine via different routes of administration

Abstract

A novel bivalent opioid tetrapeptide, biphalin (Tyr-D-Ala-Gly-Phe-NH)2, was synthesized based on structure-activity relationships. The analgesic activity of biphalin was assessed in comparison to morphine in rats. Drugs were administered subcutaneously (s.c.), intravenously (i.v.) and intrathecally (i.t.). Tail flick and tail pinch were used as tests for analgesia. Biphalin s.c. showed negligible analgesic activity, but when given i.v. produced significant analgesia, although less potent than morphine via this route. In contrast, intrathecal biphalin was more potent than morphine. These results indicate that biphalin has intrinsic activity that is compromised by enzymatic degradation or redistribution in the periphery, properties that may render it useful in exploring analgesic actions of locally applied opioids in the periphery without the likelihood of unwanted central effects.

Modulation Between High- and Low-Frequency Transcutaneous Electric Nerve Stimulation Delays the Development of Analgesic Tolerance in Arthritic Rats

“…This peptide also produces antinociceptive effects comparable with morphine after systemic injection and has been shown to produce less dependence than morphine on chronic use. 50,51 Similarly to biphalin, it seems that modulating frequency exerts a dual agonist action at μ-and δ-opioid receptors which has been shown to cause a delay in the development of tolerance to TENS treatment.…”

Biphalin, a Dimeric Enkephalin, Alleviates LPS-Induced Activation in Rat Primary Microglial Cultures in Opioid Receptor-Dependent and Receptor-Independent Manners

“…It was shown that biphalin has high affinity to mu opioid receptor (MOP) and delta opioid receptor (DOP) but lower affinity to kappa opioid receptor (KOP) [11, 12]. An antinociceptive character of biphalin was documented in an animal model of cancer pain [13], a semichronic colitis model [14], and in naïve animals [15, 16]. Biphalin exhibits 1000-fold greater analgesic potency than morphine [17, 18] and produces less side effects [17].…”

Stable Biodegradable Polymers for Delivery of Both Polar and Non-Polar Drugs. Phase I

“…Several other analgesics are also available with similar potencies for which similar calculations could be made. As with hydromorphone, the drugs listed below may be delivered intramuscularly (IM) or subcutaneously (SC) (PDR, 1994;Beaver, 1980 It is to be noted that recent work with opioid peptides (Silbert et al, 1991;Misterek, 1994) indicates that these are also highly potent analgesics. On the other hand, the choice of hydromorphone for this study was based on several considerations.…”

“…Measurements were taken prior to implantation to establish base line data and following implantation at 0.5 hrs, and subsequently at days 2, 4, 7, and 8 or 9. The percent of maximum analgesic response (% MAR) was calculated from the following equation (Silbert et al, 1991).…”