SR-14968 is a novel small-molecule compound designed to target the μ-opioid receptor (MOR) in a G protein-biased manner. Unlike conventional opioids that indiscriminately activate both the G protein and β-arrestin pathways, SR-14968 preferentially activates the G protein signaling cascade while minimizing β-arrestin recruitment. This unique signaling bias underpins its analgesic potency and reduced side effect profile, making it a highly attractive candidate for further pharmaceutical research into safer opioids.

Chemical Information

• IUPAC Name: 3-[1-[1-(4-bromophenyl)ethyl]piperidin-4-yl]-5,6-dichloro-1H-benzimidazol-2-one

• Molecular Formula: C₂₀H₂₀BrCl₂N₃O

• Molecular Weight: 469.2 g/mol

• CAS Number: 2133455-40-8

• Appearance: Off-white to pale beige crystalline solid

• Purity: ≥98% (HPLC)

Mechanism of Action

SR-14968 is classified as a biased agonist at the μ-opioid receptor (MOR), which is a G protein-coupled receptor (GPCR). When endogenous or exogenous opioids bind to MOR, they activate two major intracellular signaling cascades:

• G Protein Pathway: Associated with analgesia and euphoria

• β-Arrestin Pathway: Linked to respiratory depression, constipation, tolerance, and dependence

SR-14968 displays a strong bias toward G protein signaling, significantly reducing activation of the β-arrestin 2 pathway. This selective engagement enhances therapeutic benefits while minimizing life-threatening side effects.

Pharmacological Profile

Analgesic Efficacy

Preclinical models have shown that SR-14968 provides potent pain relief, comparable to or exceeding that of morphine. It has been tested in standard nociceptive models such as the tail-flick and hot-plate assays, demonstrating efficacy in acute and inflammatory pain.

Reduced Side Effects

Due to its selective G protein bias, SR-14968 produces:

• Lower respiratory depression

• Reduced constipation

• Slower development of tolerance

• Less physical dependence

In animal models, even high doses did not trigger the same level of respiratory suppression seen with morphine or fentanyl.

Dosage Guidelines (For Research Use Only)

• Rodent Models: Effective range 0.3 mg/kg – 3 mg/kg (IP or SC)

• Human Equivalent Dose: Not established — strictly not for human consumption

• Suggested Solvents: DMSO, ethanol, or saline-based buffers with appropriate co-solvents

All research must comply with ethical guidelines. This compound is not approved for clinical use in humans.

Pharmacokinetics (Predicted)

• Bioavailability: Presumed high due to lipophilic groups

• Onset of Action: Within 15–30 minutes (animal data)

• Duration: 3–5 hours

• Metabolism: Hepatic (CYP450 likely involved)

• Excretion: Renal and biliary pathways (to be confirmed)

Adverse Effects

Although SR-14968 significantly mitigates some classic opioid side effects, the following have been observed in laboratory conditions:

• Mild sedation

• Transient hypotension

• Decreased GI motility (less than morphine)

• Psychological dependence potential with chronic use

Harm Reduction Considerations

Given SR-14968’s action at the μ-opioid receptor:

• Do not mix with CNS depressants (alcohol, benzos)

• Use precision equipment for accurate dosing

• Store securely, clearly labeled “NOT FOR HUMAN USE”

• Dispose responsibly to prevent environmental contamination

• Avoid vaporization or insufflation, which may alter compound stability

Legal Status

As of the current date, SR-14968 is not scheduled under international conventions. However, local regulations may vary. Researchers are advised to verify regional laws before procurement or transport.

Conclusion

SR-14968 represents a promising new class of opioids that offers robust analgesia while addressing major safety issues inherent to traditional opioids. Its selective bias for G protein signaling introduces a pharmacological advantage with broad applications for pain research, neuropharmacology, and biased agonism modeling.