tezampanel (LY-293558) / Proniras Corp, Amgen - LARVOL DELTA

The Limited Efficacy of Midazolam in Comparison with Tezampanel and Caramiphen Against Nerve Agent-Induced Status Epilepticus and Brain Damage: Evaluation of SUDEP (AES 2025) - "For the treatment of nerve agent-induced status epilepticus (SE), the FDA has approved the use of benzodiazepines—initially diazepam and recently midazolam (MDZ); however, benzodiazepines are not neuroprotective, particularly if not administered promptly. The results suggest that MDZ treatment may carry higher risks for males. Replacing benzodiazepines with antiglutamatergic first-line treatments to prevent long-term brain damage and associated morbidities is overdue; LY293558+CRM has produced the most promising results reported so far."

Clinical • Cardiovascular • CNS Disorders • Epilepsy • Immunology • Infectious Disease • Mood Disorders • Psychiatry • Vascular Neurology

Sex-dependent differences in the antiseizure and neuroprotective effects of midazolam after soman exposure: Superior, sex-independent efficacy of tezampanel and caramiphen. (PubMed, Exp Neurol) - "For the treatment of nerve agent-induced status epilepticus (SE), the FDA has approved the use of benzodiazepines-initially diazepam and recently midazolam (MDZ); however, benzodiazepines are not neuroprotective, particularly if not administered promptly. The results suggest that MDZ treatment may carry higher risks for males. Replacing benzodiazepines with antiglutamatergic first-line treatments to prevent long-term brain damage and associated morbidities is overdue; LY293558 + CRM has produced remarkably promising results."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • Vascular Neurology

Study to Assess the Use of Tezampanel for Opioid Withdrawal Syndrome in Treatment-Seeking Patients With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Proniras Corporation | Not yet recruiting ➔ Recruiting

Enrollment open • Substance Abuse

Study to Assess the Use of Tezampanel for Opioid Withdrawal Syndrome in Treatment-Seeking Patients With Opioid Use Disorder (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Proniras Corporation

New P1 trial • Substance Abuse

Preventing Long-Term Brain Damage by Nerve Agent-induced Status Epilepticus in Rat Models Applicable to Infants: Significant Neuroprotection by Tezampanel Combined with Caramiphen but not by Midazolam Treatment. (PubMed, J Pharmacol Exp Ther) - "Significance Statement To protect the brain and the lives of infants in the event of mass exposure to nerve agents, an anticonvulsant treatment must be administered that will effectively stop seizures and prevent neuropathology, even if it is offered with a relative delay after seizure onset. The present study shows that midazolam, which was recently approved by the FDA for the treatment of nerve agent-induced status epilepticus, is not an effective neuroprotectant, while brain damage can be prevented by targeting glutamate receptors."

Journal • Preclinical • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • Vascular Neurology

Delayed tezampanel and caramiphen treatment but not midazolam protects against long-term neuropathology after soman exposure. (PubMed, Exp Biol Med (Maywood)) - "Spontaneous recurrent seizures appeared only in midazolam-treated rats, at three and six months postexposure in males and only at six months in females. These findings suggest that delayed treatment of nerve agent-induced SE with midazolam may result in long-lasting or permanent brain damage, while antiglutamatergic anticonvulsant treatment consisting of tezampanel and caramiphen may provide full neuroprotection."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • Vascular Neurology

Neurotoxicity evoked by organophosphates and available countermeasures. (PubMed, Arch Toxicol) - "Encouraging results have been reported for tezampanel, an antagonist of GluK1 kainate and AMPA receptors, especially in combination with caramiphen, an anticholinergic and anti-glutamatergic agent. On the other hand, targeting ROS by antioxidants cannot or already developed neuroinflammation does not seem to be very productive as other processes are also involved."

Journal • Review • CNS Disorders • Epilepsy • Immunology • Inflammation • Mental Retardation • Psychiatry

Antiseizure and Neuroprotective Efficacy of Midazolam in Comparison with Tezampanel (LY293558) against Soman-Induced Status Epilepticus. (PubMed, Toxics) - "Diazepam is approved by the FDA for the treatment of nerve agent-induced SE, and midazolam (MDZ) is currently under consideration to replace diazepam. The rats treated with LY293558 did not differ from the control rats (not exposed to soman) in any of these measurements. Thus, LY293558 has significantly greater efficacy than midazolam in protecting against prolonged seizures and brain damage caused by acute nerve agent exposure."

Journal • CNS Disorders • Epilepsy • Mood Disorders • Psychiatry • Vascular Neurology

Superior antiseizure and neuroprotective efficacy of LY293558-Caramiphen in combination when compared to midazolam against soman induced seizures in 7 days old rats (Neuroscience 2021) - "The appearance/incidence of spontaneous recurrent seizures was greater in the MDZ-treated group, and the difference from the LY293558+CRM group reached statistical significance at the 3-month time point. The combined administration of LY293558 and caramiphen, by blocking mainly AMPA, GluK1, and NMDA receptors, is a very effective anticonvulsant and neuroprotective therapy against soman in immature rats.; Grant Support: NINDS Grant 1U01NS102135-01A1"

Preclinical • CNS Disorders • Mood Disorders • Psychiatry

Targeting the glutamatergic system to counteract organophosphate poisoning: A novel therapeutic strategy. (PubMed, Neurobiol Dis) - "Diazepam is the FDA-approved anticonvulsant for the treatment of nerve agent-induced SE, and its replacement by midazolam is currently under consideration. More beneficial effects and complete neuroprotection is obtained when LY293558 administration is combined with caramiphen, which antagonizes NMDA receptors. Further efficacy studies may bring the LY293558 + caramiphen combination therapy on the pathway to approval for human use."

Journal • Review • CNS Disorders • Vascular Neurology

Acetylcholinesterase inhibitors (nerve agents) as weapons of mass destruction: History, mechanisms of action, and medical countermeasures. (PubMed, Neuropharmacology) - "Treatment with diazepam or midazolam for the cessation of nerve agent-induced status epilepticus cannot protect against brain damage, and, therefore, these benzodiazepines should be replaced by novel anticonvulsants and neuroprotectants. The AMPA/GluK1 receptor antagonist LY293558 (tezampanel) has shown superior antiseizure and neuroprotective efficacy against soman, particularly when administered in combination with caramiphen, an antagonist of muscarinic and NMDA receptors."

Journal • Review • CNS Disorders • Vascular Neurology