Disease relevance of Biphalin

• In a cross-dependence study, biphalin did not suppress body weight loss after morphine withdrawal, but successfully suppressed weight loss after pentazocine withdrawal [1].
• These observations indicate that biphalin possesses anti-retroviral activity in vitro, suggesting that this opioid peptide should be examined further in vivo to determine if it is a candidate for combined therapy with AZT and possibly other drugs for retrovirus infections including the human immunodeficiency virus (HIV) [2].
• Postmortem verification of catheter placement revealed that in those rats in which high-dose biphalin did not produce analgesia or muscle rigidity, the catheter was positioned incorrectly or the flow of drug solution was obstructed [3].

High impact information on Biphalin

• Brain and spinal cord distribution of biphalin: correlation with opioid receptor density and mechanism of CNS entry [4].
• Also, a statistically greater amount of [125I-Tyr1] biphalin was detected in two other circumventricular organs, the choroid plexus and pituitary, when compared with other brain regions [4].
• The aim of the present study was to characterize and compare the blood-to-central nervous system (CNS) pharmacokinetics and biological stability of biphalin and related halogenated analogs [5].
• (2 kDa)(2) PEG-biphalin displayed an area under the curve (AUC) approximately 2.5 times that of biphalin with enhanced analgesia up to 300 min postinjection [6].
• These findings indicate that PEG conjugation to biphalin retains opioid-mediated effects observed with biphalin and is a valuable tool for eliciting potent, sustained analgesia via parenteral routes of administration [6].

Biological context of Biphalin

• Structure-activity relationship of biphalin. The synthesis and biological activities of new analogues with modifications in positions 3 and 4 [7].
• Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes [8].

Anatomical context of Biphalin

• Biphalin, an enkephalin analog with unexpectedly high antinociceptive potency and low dependence liability in vivo, selectively antagonizes excitatory opioid receptor functions of sensory neurons in culture [9].
• The radioligand binding profiles of these compounds for two types of tissues, rat brain membranes, and NG108-15 cell membranes were identical to the parent biphalin [10].
• We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production [8].
• On the other hand the binding of the dicationic biphalin ligands to membranes increases proportionally with increased negative surface charge [11].

Associations of Biphalin with other chemical compounds

• Morphine (mu-agonist), biphalin (mu- and delta-agonist), and U50488H (kappa-agonist) were administered to each group, and analgesia was measured by tail flick latency testing [12].
• This study presents the X-ray crystal structure of biphalin sulfate and compares it to other opioids that interact with the same biological targets [13].
• The observed permeabilities and partition coefficients of biphalin and analogues, as well as the tyrosine side chain accessibility, are consistent with the presence of the type of folding where the tyrosine and phenylalanine side chains are in a close contact [14].

Analytical, diagnostic and therapeutic context of Biphalin

• P85 coadministration with DPDPE and biphalin showed increased (p < 0.01) analgesia with both 0.01 and 1.0% P85 [15].
• The CNS uptake and stability of biphalin and p-[Cl-Phe4,4']biphalin was examined further using an in situ brain perfusion technique coupled to high-performance liquid chromatography analysis [5].
• Intrathecal injection of the opioid peptide biphalin (BIP) produced antinociception for over 3 hrs without neurotoxicity [16].
• This study presents the synthesis and in vitro bioassays of six new biphalin analogues with three different non-hydrazine linkers, some of which have higher binding affinity and bioactivity than biphalin [17].

References