Prialt (ziconotide) / Jazz - LARVOL DELTA

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

Intrathecal ziconotide for the treatment of chronic pain: a collection of clinical experiences and literature review. (PubMed, Eur Rev Med Pharmacol Sci) - "IT ziconotide represents a valuable addition to the armamentarium of pain management strategies, offering hope for improved quality of life for patients suffering from chronic, treatment-resistant pain. Continued research and clinical experience will further elucidate its optimal use and role in comprehensive pain care."

Journal • Review • Oncology • Pain

Ziconotide Daily Dose Predicts Neuropsychic Disorders Onset in Patients with Refractory Cancer Pain (IASP 2024) - "Both initial and maintenance intrathecal therapy included morphine, ropivacaine, and ziconotide. Ziconotide appears to be frequently involved in the occurrence of NPDs in patients receiving intrathecal analgesic therapy for refractory cancer pain. The daily dose of ziconotide found to be predictive of NPDs onset is close to its minimum therapeutic dose, highlighting its narrow therapeutic index."

Clinical • Anesthesia • CNS Disorders • Oncology • Pain

NHP SIG: Current & Future Biological Therapeutics for Managing Pain (IASP 2024) - "Monoclonal antibodies aimed at reducing over production of NGF, TNFalpha and CGRP as well as ziconotide which is a synthetic version of ω-conotoxin MVIIA (ω-MVIIA), a peptide found in the venom of the fish-eating marine snail, Conus magus, have all been approved for the treatment of chronic pain in one form or another...• Describe recent advances in the discovery and development of novel biologics and potential new targets and modalities for biologics. Young scientists will have had the opportunity to present their novel work to a broad cross section of pain researchers and clinicians, which could help them refine their ideas."

Gene Therapies • Pain • TNFA

Intrathecal Ziconotide Infusion Therapy for Oncologic Refractory Neuropathic Pain: Case Report With High-Dose Intraventricular Ziconotide After 15 Years of Treatment. (PubMed, Neuromodulation) - No abstract available

Journal • Neuralgia • Pain

Harnessing the ocean's pharmacy: marine bioactive compounds as next-generation therapeutics. (PubMed, Nat Prod Res) - "Notable examples include anticancer agents like trabectedin and cytarabine, and the analgesic ziconotide. Advances in synthetic biology and metabolic engineering provide solutions for sustainable production, ensuring a stable supply of these valuable compounds. The integration of marine bioactives into modern medicine could revolutionize treatments for cancer, chronic pain, and infectious diseases, underscoring the need for continued investment in marine bioprospecting and biotechnological innovation."

Journal • Infectious Disease • Oncology • Pain

A comprehensive review on ziconotide. (PubMed, Heliyon) - "Additionally, the review will explore the current efforts to refine the structure of ziconotide for better clinical outcomes. Lastly, it will prospect potential developments in the new class of selective N-type voltage-sensitive calcium-channel blockers."

Journal • Review • CNS Disorders • Depression • Pain • Psychiatry

Intrathecal Ziconotide for the treatment of refractory chronic pain in pelvic osteosarcoma (Euroanaesthesia 2024) - "Its primary use is intrathecal in patients with refractory oncologic pain to other analgesic measures due to its ability to inhibit the release of neurotransmitters responsible for nociception in the posterior spinal horn 2 . Initiating treatment at low doses helps prevent the occurrence of undesirable effects such as confusion, drowsiness, or mood alterations typical of this drug."

Musculoskeletal Pain • Oncology • Osteosarcoma • Pain • Palliative care • Sarcoma • Solid Tumor

A Benefit/Risk Assessment of Intrathecal Ziconotide in Chronic Pain: A Narrative Review. (PubMed, J Clin Med) - "Overall, the use of Ziconotide, as a monotherapy or in conjunction with other therapies for the treatment of chronic pain, was reported to be efficacious. Overall, its use in patients with chronic pain refractory to other pharmacologic agents outweighs the possible adverse consequences, thus resulting in a favorable benefit/risk assessment."

Benefit-risk assessment • Journal • Review • CNS Disorders • Mental Retardation • Neuralgia • Pain • Psychiatry

Physicochemical Stability Study of the Morphine-Bupivacaine-Ziconotide Association. (PubMed, Neuromodulation) - "All results are in favor with a physicochemical stable preparation for six mixture profiles when stored in polypropylene syringes at 5 °C ± 3 °C and 25 °C ± 2 °C. For mixtures stored in implantable pumps, the efficacy should decrease over time owing to the degradation of ziconotide. A trade-off between high morphine concentration and increased refill interval will need to be found by clinicians."

Journal • Oncology • Pain