Prialt (ziconotide) / Jazz - LARVOL DELTA

Recent Applications of Disulfide Bond-Containing Compounds in Medicinal and Agrochemical Chemistry. (PubMed, J Agric Food Chem) - "In the medical field, disulfide bonds are crucial for stabilizing bioactive molecules like insulin and ziconotide, enhancing their efficacy...However, challenges like low large-scale synthesis efficiency, poor agrochemical field stability, resistance risks, and unclear environmental fate remain. The study concludes that optimizing synthesis, developing stable formulations, and exploring controllable disulfide bond technologies will further unlock the potential of these compounds, driving progress in human health and sustainable agriculture."

Journal • Review

Efficacy and safety of the Cav2.2 blocker Ziconotide in pain: a meta-analysis and systematic review. (PubMed, Pain Rep) - "Although Ziconotide shows promise as an intrathecal treatment for refractory pain, its frequent adverse effects, the availability of high-certainty evidence, and inconclusive impact on opioid consumption highlight the need for cautious use. This meta-analysis underscores the need for future research."

Journal • Retrospective data • Review • Pain • CACNA1B • CAV2

Ziconotide as an Opioid Rescue: Economic, Clinical, and Subgroup Considerations [Letter]. (PubMed, J Pain Res) - No abstract available

Journal

A Case of Abrupt Cessation of Intrathecal Clonidine (ASRA-FALL 2025) - "Case Presentation: A 70-year-old man with refractory neuropathic pain secondary to bilateral lower-extremity complex regional pain syndrome was managed with an intrathecal drug delivery system infusing fentanyl (350 mcg/day), ziconotide (6.56 mcg/day), and clonidine (450 mcg/day)...The 3 FDA approved intrathecal medications include morphine, baclofen, and ziconotide...Once stabilized after 72 hours, he was transitioned to the medical floor with as-needed oral hydralazine and continuation of oral and transdermal clonidine...In this case, the patient’s opioid withdrawal was effectively managed with oral methadone 5 mg TID...Outcome: The patient's infection resolved with targeted antibiotics. Clonidine withdrawal was successfully managed with combination of oral and transdermal clonidine followed by taper schedule on hospital discharge (tapered off oral clonidine first then transdermal clonidine)."

Clinical • Late-breaking abstract • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Dermatology • Gastrointestinal Disorder • Hypertension • Infectious Disease • Musculoskeletal Pain • Neuralgia • Psychiatry

Directing the oxidative folding of disulfide-rich peptides for enhanced engineering and applications. (PubMed, Chem Sci) - "These attributes drive their utility as high-affinity molecular tools in bioanalytics/chemical biology and clinically validated therapeutics (e.g., ziconotide for chronic pain and insulin for diabetes)...Herein, we summarize novel strategies that actively direct the oxidative folding of DRPs to enhance their engineering and applications. Additionally, we present our perspective on key challenges in DRP design and discovery associated with oxidative folding, and propose future research directions to advance this field."

Journal • Review • Diabetes • Metabolic Disorders • Pain

Can Ziconotide Be Used to Replace Opioids? Exploratory Clinical Experience in 5 Patients Treated in the Pain Unit. (PubMed, J Pain Res) - "Intrathecal opioid rescue with ziconotide emerges as a viable therapeutic option for patients with refractory pain and a neuropathic component, or for those who develop adverse events associated with IT morphine. Low doses and slow titration of ziconotide may help minimize adverse events while maintaining analgesic benefit."

Journal • Colon Cancer • Colorectal Cancer • Constipation • Endocrine Disorders • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Musculoskeletal Pain • Oncology • Osteosarcoma • Pain • Sarcoma • Solid Tumor

The role and behavior of voltage-gated calcium channels annels in ischemia/reperfusion. (PubMed, Cell Signal) - "Experimental studies demonstrating the protective effects of VGCC inhibitors-such as nimodipine, mibefradil, and SNX-111-are critically evaluated along with their translational limitations. By integrating up-to-date mechanistic insights with preclinical and early clinical data, this review highlights VGCCs as promising molecular targets for preventing I/R injury. Future therapeutic strategies should focus on isoform-specific targeting, time-dependent administration, and organ-directed formulations to enhance efficacy and safety."

Journal • Review • Cardiovascular • Metabolic Disorders • Reperfusion Injury

Animal Venom in Modern Medicine: A Review of Therapeutic Applications. (PubMed, Toxins (Basel)) - "Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders."

Journal • Review • Cardiovascular • Hematological Disorders • Infectious Disease • Oncology • Pain • Thrombosis

Spinal analgesia in cancer pain management-MASCC general practice recommendations. (PubMed, Support Care Cancer) - "Morphine and hydromorphone are the opioids of choice for IT treatment...Ziconotide requires a slow dose titration, but it can be used in small volumes...The use of boluses of hydrophilic opioids, like morphine, for treating breakthrough pain may be inadequate, as intrathecal opioids alone may be unable to adequately treat an episode of rapid pain onset and duration. The decision-making process for employing interventional therapies, like spinal analgesia, should be shared, taking into account the actual indications and needs, previous treatments, prognosis, timing, advantages and disadvantages, and complications, in any individual situation, managing all the aspects of care."

Journal • Review • Anesthesia • Oncology • Pain • Palliative care

Recurrent Ziconotide-Associated Delirium and Psychosis: A Case Report. (PubMed, J Clin Psychopharmacol) - No abstract available

Journal • CNS Disorders • Psychiatry

Cerebrospinal Fluid Flow Enhancement (CFE) Increases the Spatial Distribution of Methotrexate after Intracerebroventricular Administration in a Sheep Model. (PubMed, Mol Pharm) - "As of 2024, only a handful of drugs are FDA-approved for CSF administration, including morphine, baclofen, ziconotide, and methotrexate. This hypothesis was tested with a recirculating device, which we used to continuously recirculate fluid from the intracerebral lateral ventricles (ICV) to the cisterna magna (CM). Our experimental results provide detailed maps of the spatial distribution of MTX following CSF administration in sheep and support our expectation that CFE is an effective method to manipulate CNS drug distribution."

Journal • Brain Cancer • CNS Tumor • Oncology

Neuropsychiatric symptoms induced by intrathecal ziconotide: case reports (Euroanaesthesia 2025) - "After implanting an intrathecal morphine pump, ziconotide was added at 1.31mcg/day and titrated to 7.5mcg/day over 11 months, improving pain...An intrathecal ziconotide pump (1.2mcg/day) was implanted, later combined with baclofen...Patient profiles and neuropsychiatric presentations were heterogeneous. Many times, symptom resolution required drug discontinuation."

Case report • Clinical • Cardiovascular • Central Neuropathic Pain • CNS Disorders • Hypertension • Malignant Pleural Mesothelioma • Mesothelioma • Musculoskeletal Pain • Neuralgia • Oncology • Pain • Pleural Mesothelioma • Psychiatry • Solid Tumor • Suicidal Ideation • Vascular Neurology

INTRATHECAL DRUG PUMPS & ITS CHALLENGES: HOW TO PROCEED & IMPLICATIONS IN OUR PRACTICE (ASRA-SPRING 2025) - "Stage 1 - Patient Admission: • 73-year-old male w/ PMHx of CAD, CKD Stage 3, chronic PVD (s/p fem-pop bypass on 4/2024) on Xarelto, HTN • Recently incarcerated • Altered Mental Status (AMS) concerning for septic shock 2/2 pneumonia vs. Pseudomonas UTI • Intrathecal drug delivery system (IDDS) in situ, unknown contents Stage 2 – Initial Assessment & Concerns: • Our service was consulted d/t thoughts that pump may have contained Baclofen. Baclofen withdrawal could be contributing/causing AMS • Baclofen withdrawal is a life-threatening emergency • Limited medical records; patient unable to provide history d/t AMS • Differential: septic shock vs IDDS withdrawal Stage 3 – Diagnostic & Investigative Steps: • Pain consult to identify IDDS contents • Radiographic analysis → IDDS confirmed • Specialized equipment (pump interrogator) unavailable (company defunct) • Via PDMP review: Fentanyl 5000 mcg/mL, 1430 mcg/24 hrs w/ PTM dose of 80 mcg over 3 minutes, q1hour lockout..."

Chronic Kidney Disease • CNS Disorders • Epilepsy • Infectious Disease • Insomnia • Movement Disorders • Neuralgia • Oncology • Pain • Pneumonia • Psychiatry • Respiratory Diseases • Septic Shock • Sleep Disorder

Dilution of Ziconotide for Intrathecal Trial: The Effect of Dilution on the Incidence of Side Effects and Pain Relief: A Single-center Retrospective Case-control Study. (PubMed, Pain Physician) - "This study demonstrates there is no substantial difference between diluted and undiluted bolus doses of intrathecal ziconotide in regard to analgesic effect or side effects."

Adverse events • Journal • Retrospective data • Pain

A Simple Approach to Assign Disulfide Connectivity for Ziconotide via Partial Reduction Without Alkylation. (PubMed, Rapid Commun Mass Spectrom) - "A relatively simple method based on partial reduction without alkylation, followed by analysis with liquid chromatography-tandem mass spectrometry, was developed, assigning disulfide connectivity for a disulfide-rich peptide. This method is useful in the quality control of medicinal peptides with an extensive disulfide network."

Journal

An Intrathecal Pump Misadventure in Two Acts: An Unrecognized Partial Pocket Fill Followed by an Unusual Withdrawal Syndrome Two Months Later. (PubMed, J Palliat Med) - "Eight weeks prior, her intrathecal pump was refilled with morphine, bupivacaine, and ziconotide. This case represents an example of both an unrecognized partial pocket fill and an atypical presentation of opioid withdrawal manifesting as akathisia. Furthermore, this patient's case may be considered a medical error given the serious morbidity that can be associated with inadvertent pocket fills."

Journal • Anesthesia • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models. (PubMed, J Clin Invest) - "Antagonists (e.g., Ziconotide, Gabapentin) of the CaV2.2 (N-type) calcium channels are used clinically as analgesics for chronic pain. C2230 also decreased fiber photometry-based calcium responses in the parabrachial nucleus, mitigated aversive behavioral responses to mechanical stimuli after neuropathic injury, and preserved protective pain responses, all without affecting motor or cardiovascular function. Finally, site-directed mutation analysis demonstrated that C2230 binds differently than other known CaV2.2 blockers, making it a promising lead compound for analgesic development."

Journal • Cardiovascular • Osteoarthritis • Pain • CACNA1B • CAV2

AISA 021, a Novel Calcium Channel Antagonist in Development for Raynaud's & Systemic Sclerosis, Has Antagonistic Activity at Sodium Channel Targets for Pain Relief and Treats Scleroderma Pain Better Than Current Calcium Channel Blockers in a Phase 2A Study (ACR Convergence 2024) - "An N-type antagonist, ziconotide, is approved for neuropathic pain...Cilnidipine at the clinical concentration obtained from pk samples in the ongong Phase 2A study was found to more potently inhibit Nav1.7 in the closed state than gabapentin, amlodipine and bupivacaine, at similarly clinically relevant plasma concentrations...On the pain domain of the SHAQ, cilnidipine 10 mg(n=4) reduced pain by 27% but 62% with tadalfil 5 mg(n=5) , 20 mg(n=3) increased pain 12% but decreased pain 24% with tadalafil 5 mg(n=4), and placebo patients(n=4) reduced pain 4%... Cilnidipine seems to have clinically relevant inhibitory properties at Nav 1.7 and may have this at Nav 1.8 as well, based on structure activity relationship analysis and pending experimental determination. In a preliminary Phase 2 study, encouraging effects were seen in pain relief as reported by patients in addition to a reduction in the weekly frequency of Raynaud's attacks. Clinicians often combine a CCB with a..."

P2a data • Cardiovascular • Immunology • Neuralgia • Pain • Rheumatology • Scleroderma • Systemic Sclerosis • NAV1

Ziconotide and psychosis: from a case report to a scoping review. (PubMed, Front Mol Neurosci) - "On the other hand, 13 papers were retrieved from the scoping review (9 case reports, 4 case series), which included 21 cases of patients treated with ziconotide who presented adverse effects ranging from psychotic symptoms to delirium. In conclusion, the variety of neuropsychiatric symptoms derived from ziconotide could be related to the blockade of N-type voltage-gated calcium channels in glutamatergic and GABAergic neurons, in turn affecting dopaminergic pathways."

Journal • Review • CNS Disorders • Pain • Psychiatry

The Diagnosis and Treatment of Neuropathic Pain. (PubMed, Dtsch Arztebl Int) - "The treatment of neuropathic pain can be either cause-directed or symptom-directed, depending on its origin. Multidisciplinary collaboration can facilitate both the diagnostic evaluation and the selection of the optional modality and timing of treatment."

Journal • Review • Anesthesia • Neuralgia • Oncology • Pain

Skin-derived recombinant hiPSC chromaffin cells releasing MVIIA-serine-histogranin construct grafted with enhanced PEG biomatrix attenuates chronic SCI pain (Neuroscience 2024) - "Our previous findings indicated the efficacy of the N-type Ca2+ channel blocker omega conopeptide MVIIA (known as Prialt) and NMDA antagonist serine-histogranin (SHG) in various pain models...The presence of grafted cells and recombinant peptides was confirmed in the spinal tissue. These findings showed the promise of using PEG as a biomatrix for intrathecal cell grafting and further indicated that recombinant hiPSC-derived chromaffin cells can enhance effectiveness of hCC transplantation in chronic pain management."

CNS Disorders • Pain

Determination of related substances in disulfide-rich peptide ziconotide by establishing tandem mass spectrometry methods. (PubMed, J Pharm Anal) - "Image 1."

Journal

SPIDOL study protocol for the assessment of intrathecal ziconotide antalgic efficacy for severe refractory neuropathic pain due to spinal cord lesions. (PubMed, Trials) - "A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period."

Clinical protocol • Journal • Central Neuropathic Pain • CNS Disorders • Neuralgia • Orthopedics • Pain

Real-World Prescription Data for Intrathecal Drug Delivery: A Retrospective Analysis in 32,784 Patients. (PubMed, Neuromodulation) - "Despite the prevalence of IDDS for managing chronic, intractable pain, minimal data exist on real-world prescription practices. Our study found that FDA-approved IT formulations accounted for the minority of prescriptions, indicating significant practice variation, with off-label prescriptions being common."

Journal • Real-world • Real-world evidence • Retrospective data • Pain

Natural pain killers from marine sources: a new frontier in neurosurgical pain management. (PubMed, Neurosurg Rev) - "The analgesic potential of marine-derived peptides, alkaloids, terpenes and polyketides-such as discodermolide from marine sponges and ziconotide from cone snail venom-is highlighted in this letter. These substances work through novel methods that minimize the negative effects associated with conventional analgesics while focusing on particular pain pathways. Despite obstacles in sustainable sourcing and regulatory validation, the development of these marine-derived analgesics requires interdisciplinary collaboration to fulfill their potential in enhancing pain management."

Journal • Review • Pain