The pain management field is currently driven by the urgent need to move beyond addictive opioids and treatment options than run the risk of toxicity at high doses, such as acetaminophen (APAP) and nonsteroidal anti-inflammatory drugs (NSAIDs). SRP-001, a novel compound that is metabolized into a nontoxic agent, offers a compelling alternative. Researchers recently used single-cell multiomics to determine its mechanism of action within the brain region responsible for pain sensation, demonstrating the drug’s potential as a favorable option to APAP.1
Hernan Bazan, MD, FACS Cofounder and Chief Executive Officer South Rampart Pharma, Inc.
In this Innovation Spotlight, Hernan Bazan, the cofounder and chief executive officer of South Rampart Pharma, explains how SRP-001 works, what makes it different, and why its development represents a meaningful shift in the field.
What is the current state of pain management, and what are some of the most urgent unmet needs?
There is a critical unmet need for the development of analgesics that lack the addictive effects of opioids and the dose-limiting toxicities of APAP and NSAIDs. The FDA approval of Vertex Pharmaceuticals' Journavx (suzetrigine) in early 2025 was a landmark event for the entire pain sector. This approval validated voltage-gated sodium channels, found on peripheral sensory neurons, as a legitimate and commercially viable target for non-opioid pain relief, ending a decades-long search for a new mechanism in acute pain. However, the clinical failure of a subsequent sodium channel inhibitor has made it clear that this approach may not be appropriate in all situations. The mixed outcomes surrounding this new class of analgesics suggest that they may not be the one-size-fits-all solution in pain relief that many had hoped for. Given the variety of causal factors involved in acute and chronic pain, there is a need to develop additional pain relief drugs that act across differing mechanisms and can be used synergistically or in differing use cases.
What was the motivation behind developing SRP-001, and how does it address the limitations of current painkillers?
As a practicing surgeon, I witnessed the need for better pain relief alternatives firsthand. Patients are currently left with limited options, as existing painkillers carry undesirable effects such as addiction and toxicity. SRP-001 was developed to address this critical need. Importantly, SRP-001 was designed to circumvent the addictive nature of opioids and acts through a mechanism of action that has not been associated with dependence or abuse potential. Additionally, the drug candidate was designed to avoid toxicities that are often observed with chronic and high-dose administrations of APAP and NSAIDs. It is also important to note that SRP-001’s mechanism of action differs from that of suzetrigine, in that SRP-001 acts via a central mechanism in a region of the brain that is associated with pain sensation.2 Conversely, suzetrigine acts on peripheral nerve fibers and may not be appropriate for all types of pain.3
How does SRP-001 work, and how did researchers discover its mechanism?
SRP-001 is metabolized into AM404, an active compound that increases endocannabinoid signaling in the midbrain periaqueductal gray (PAG), a key brain region involved in pain perception. AM404 inhibits anandamide uptake to increase the brain’s endogenous cannabinoid activity and engages pain-regulating receptors such as TRPV1 and CB1. SRP-001’s mechanism of action is similar to that of APAP but avoids the generation of the toxic byproduct N-acetyl-p-benzoquinone imine (NAPQI) that is responsible for APAP-induced liver injury.
SRP-001 was jointly discovered by a colleague who is a medicinal chemist at the University of Alca and researchers at Louisiana State University Health Sciences Center New Orleans, who used a rational, structure-based drug design strategy to eliminate NAPQI formation while preserving analgesic activity.2
Single-cell multiomic sequencing highlighted SRP-001’s molecular mechanism on a cell-by-cell basis.
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In your new study, how did SRP-001 compare to traditional pain relievers?
SRP-001 and APAP both demonstrated similar genomic and epigenomic activation patterns in the PAG, indicating a shared mechanism of action between the two pain relief agents.1 Importantly, SRP-001 has not been associated with the formation of the toxic liver metabolite NAPQI, which severely limits the use of APAP. A previous study demonstrated that SRP-001 and APAP both possess similar potency in preclinical models of acute pain relief. Additionally, SRP-001 exhibited similar efficacy to pregabalin (Lyrica®) for neuropathic pain. Collectively, these findings demonstrate that SRP-001 can elicit pain relief in a similar manner to APAP, but without the problematic liver toxicity. These results validate that the drug performs exactly as it was designed to.
What role did single-cell multiomic sequencing play in this study?
Single-cell multiomic sequencing provided a cell-specific map of how pain and analgesics affect the brain at both the level of gene expression and epigenetic changes. It revealed that SRP-001 and APAP not only share common molecular mechanisms in the PAG but also restore disrupted transcription factor activity and synaptic signaling in a highly cell-specific manner. The primary significance of using single-cell multiomic technology in a study such as this is to provide us with a greater level of detail on a cell-by-cell basis. This allows us to really understand the mechanism of pain relief on a highly granular level.
Did the results provide any new insights into pain relief pathways?
The study reveals that pain relief produced by APAP and SRP-001 analgesic treatments involves restoring protective transcription factor activity, suppressing pro-inflammatory regulators, and repairing disrupted synaptic communication. Importantly, the study provides an unprecedented level of detail with respect to how these drugs produce pain relief at the genomic and epigenomic levels within each of the various types of cells found in the brain. These results provide not only important mechanistic information with respect to the drugs that were studied but also provide additional information that could aid in the future development of additional analgesic agents. It is possible that the gene expression and epigenetic activity observed may provide an additional benefit in chronic conditions, such as neuropathic pain, beyond the acute component of the analgesic effects.
Given these promising results, what does the future hold for SRP-001 and improved pain management?
SRP-001 is ready to begin advancing through a Phase 2 clinical trial for acute post-surgical pain and will subsequently be expanded into chronic and neuropathic pain indications. Beyond that, SRP-001 would move into pivotal Phase 3 trials and later be developed into an additional formulation for intravenous administration. Ultimately, the goal is to continue advancing SRP-001 all the way into the hands of patients who desperately need nonaddictive and nontoxic alternatives to the existing pain relief treatments that are currently available.
- Bazan HA, et al. A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region. Neurobiol Pain. 2025;18:100192.
- Bazan HA, et al. Transcriptomic signature, bioactivity and safety of a non-hepatotoxic analgesic generating AM404 in the midbrain PAG region. Sci Rep. 2024;14(1):11103.
- Peshin S, et al. Pharmacology update: Suzetrigine: a novel NaV1.8 sodium channel inhibitor for acute pain management. Am J Hosp Palliat Care. 2025:10499091251353455.
