| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
Biphalin acetate targets micro-opioid, delta-opioid, and kappa-opioid receptors (ORs). As a dimeric enkephalin analog, it contains two active enkephalin pharmacophores, allowing it to bind with high affinity (Ki in the nM range) to micro- and delta-ORs. Activation of these receptors (Gi/o-coupled GPCRs) inhibits adenylyl cyclase, reduces cAMP, and activates potassium channels, leading to neuronal hyperpolarization and reduced neurotransmitter release. This results in potent antinociception. Biphalin also shows low addiction potential and physical dependence compared to morphine.
|
|---|---|
| ln Vitro |
Biphalin acetate is a potent opioid receptor agonist with Ki values in the nanomolar range for micro- and delta-opioid receptors. It is a dimeric enkephalin analog with high antinociceptive activity, reportedly over 1000-fold more potent than morphine in some assays. The compound shows analgesic effects in vitro, as measured by inhibition of cAMP accumulation in CHO cells expressing micro- or delta-ORs. EC₅0 values for cAMP inhibition are in the low nanomolar range. It also shows anti-inflammatory and antiviral activity.
|
| ln Vivo |
In vivo, Biphalin acetate crosses the blood-brain barrier and produces significant analgesic effects in acute (tail-flick, hot plate), neuropathic (chronic constriction injury), and chronic pain models. It shows reduced physical dependence liability compared to morphine in withdrawal studies. It also lowers mean arterial pressure in spontaneously hypertensive rat models of hypertension. The compound is administered by intracerebroventricular (ICV) or intravenous (IV) injection in rodent models. Doses in the range of 0.1-10 mg/kg produce significant effects.
|
| Enzyme Assay |
Opioid receptor binding (IC₅0 and Ki) is determined by radioligand binding. Membranes from cells expressing micro-, delta-, or kappa-opioid receptors are incubated with [3H]-DAMGO (micro-selective), [3H]-DPDPE (delta-selective), or [3H]-U69593 (kappa-selective) and varying concentrations of Biphalin acetate in binding buffer (50 mM Tris-HCl pH 7.4, 1 mM EDTA, 5 mM MgCl2, 0.1% BSA). Bound radioactivity is separated by filtration, and IC₅0 values are calculated. Ki is determined using the Cheng-Prusoff equation. Potency >1000-fold higher than morphine.
|
| Cell Assay |
Cellular cAMP accumulation assay: CHO cells stably expressing micro- or delta-opioid receptors are seeded in 96-well plates and treated with Biphalin acetate (0.001-1000 nM) and 10 uM forskolin to stimulate cAMP production. After 30 min at 37degC, intracellular cAMP is quantified by ELISA or HTRF. EC₅0 for cAMP inhibition is calculated. For antiviral assays, cells infected with viruses (e.g., HIV) are treated with Biphalin, and viral replication is quantified by p24 ELISA or RT-qPCR. For neuroprotection, primary cortical neurons are treated with Biphalin and exposed to excitotoxic glutamate.
|
| Animal Protocol |
Acute pain (tail-flick test): Male CD-1 mice (20-25 g, n=8-10/group) are injected ICV or IV with Biphalin acetate (0.1-10 mg/kg). Latency to tail flick from a radiant heat source is measured at 15, 30, 60, 90 min post-injection. Analgesic effect is expressed as % maximal possible effect (%MPE). Neuropathic pain (chronic constriction injury model): Adult male Sprague-Dawley rats are anesthetized, and the sciatic nerve is loosely ligated with chromic gut sutures. After 7-14 days, Biphalin is administered IP or IV (1-10 mg/kg). Mechanical allodynia is measured by von Frey filaments, and thermal hyperalgesia by Hargreaves apparatus. Antihypertensive effect: spontaneously hypertensive rats (SHR) are injected with Biphalin (1-5 mg/kg IV), and mean arterial pressure is monitored by a tail-cuff or telemetry.
|
| ADME/Pharmacokinetics |
Biphalin acetate can cross the blood-brain barrier following systemic administration. The elimination half-life in plasma is relatively short (30-60 min) due to proteolytic degradation. In the central nervous system, the half-life is longer (1-2 hours) due to protection from plasma peptidases. The compound is metabolized by peptidases (e.g., aminopeptidases, neutral endopeptidase) in the blood, liver, and brain. The acetate salt form enhances solubility. The low addiction potential is attributed to its mixed micro/delta agonist profile.
|
| Toxicity/Toxicokinetics |
Biphalin acetate has a favorable safety profile compared to morphine, with reduced physical dependence, less tolerance development, and less respiratory depression. In rodent models, it does not suppress body weight loss after morphine withdrawal in cross-dependence studies. The compound may cause mild sedation at high doses but does not show significant gastrointestinal side effects (constipation). Standard safety precautions for handling potent opioids apply: use PPE, work in a fume hood, avoid inhalation and skin contact.
|
| References |
|
| Additional Infomation |
Biphalin acetate is a research-grade synthetic opioid peptide with high potency, BBB permeability, and low addiction potential. It is used in pain research and for studying opioid receptor pharmacology. It is not an FDA-approved drug. For research use only, not for diagnostic or therapeutic applications.
|
| Molecular Formula |
C46H56N10O10.XC2H4O2
|
|---|---|
| Molecular Weight |
909.00 (free base)
|
| Related CAS # |
Biphalin TFA; 126872-95-5
|
| Sequence |
Tyr-{dAla}-Gly-Phe-NH2 (covalent bridge:Phe-Phe, dimer)Y-{D-Ala}-GF-NH2 (covalent bridge:Phe-Phe, dimer)
|
| Appearance |
Solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
