piromelatine (Neu P11) / Neurim - LARVOL DELTA

Neu-P11 Improves Type 2 Diabetes Mellitus Immune Function by Inhibiting the Hippo Signaling Pathway. (PubMed, Int J Endocrinol) - "Notably, co-treatment of Neu-P11 and XMU-MP-1 demonstrated superior restoration across all parameters, indicating the efficacy of combinatorial targeting. Neu-P11 improves immune function and increases insulin sensitivity in T2DM by inhibiting the Hippo signaling pathway, offering a novel therapeutic avenue for T2DM."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • LATS1 • SLC2A4

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress. (PubMed, Int J Mol Sci) - "The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • IR • SLC2A4

NEUP11-7: Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=225 | Active, not recruiting | Sponsor: Neurim Pharmaceuticals Ltd. | Trial primary completion date: May 2024 ➔ Jun 2025

Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia

NEUP11-7: Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=225 | Active, not recruiting | Sponsor: Neurim Pharmaceuticals Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia

Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=225 | Not yet recruiting | Sponsor: Neurim Pharmaceuticals Ltd.

New P2/3 trial • Alzheimer's Disease • CNS Disorders • Dementia

NEUP11-7: Piromelatine 20 mg in Participants With Mild Dementia Due to Alzheimer's Disease (clinicaltrials.gov) - P2/3 | N=225 | Recruiting | Sponsor: Neurim Pharmaceuticals Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Dementia

Sex-Dependent Effect of Chronic Piromelatine Treatment on Prenatal Stress-Induced Memory Deficits in Rats. (PubMed, Int J Mol Sci) - "While the ratio of phosphorylated and nonphosphorylated adenosine monophosphate response element binding protein (pCREB/CREB) was reduced in the two sexes with PNS and treated with a vehicle, the melatonin analogue elevated the ratio of these signaling molecules in the hippocampus of the male rats only. Our results suggest that Piromelatine exerts a beneficial effect on PNS-induced spatial memory impairment in a sex-dependent manner that might be mediated via the pCREB/CREB pathway."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Sex-Dependent Effects of Piromelatine Treatment on Sleep-Wake Cycle and Sleep Structure of Prenatally Stressed Rats. (PubMed, Int J Mol Sci) - "In addition, Pir increased the BDNF expression in the hippocampus in male and female offspring with PNS. Our findings suggest that the beneficial effect of Pir on PNS-induced impairment of sleep/wake cycle circadian rhythm and sleep structure is exerted via activation of MT receptors and enhanced BDNF expression in the hippocampus in male and female offspring."

Journal • Preclinical • CNS Disorders • Insomnia • Sleep Disorder • BDNF

A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer's Disease. (PubMed, J Prev Alzheimers Dis) - P2 | "The 2q12 (2:107,510,000-107,540,000) 5-6 SNPs cluster may predict efficacy of piromelatine for mild AD. These findings warrant further investigation in a larger, prospective early-stage AD clinical trial for patients who are non-carriers of the 2q12 polymorphism cluster."

Journal • Alzheimer's Disease • CNS Disorders • Dementia

Antidepressant actions of melatonin and melatonin receptor agonist: Focus on pathophysiology and treatment. (PubMed, Behav Brain Res) - "The present review summarizes the mechanisms underlying the antidepressant effects of melatonin, which is related to its functions in the regulation of the hypothalamic-pituitary-adrenal axis, inhibition of neuroinflammation, inhibition of oxidative stress, alleviation of autophagy, and upregulation of neurotrophic, promotion of neuroplasticity and upregulation of the levels of neurotransmitters, etc. Also, melatonin receptor agonists, such as agomelatine, ramelteon, piromelatine, tasimelteon, and GW117, have received considerable critical attention and are highly implicated in treating depression and comorbid disorders. This review focuses on melatonin and various melatonin receptor agonists in the pathophysiology and treatment of depression, aiming to provide further insight into the pathogenesis of depression and explore potential targets for novel agent development."

Journal • Review • CNS Disorders • Depression • Immunology • Inflammation • Mental Retardation • Psychiatry • Sleep Disorder

A Polymorphism Cluster at the 2q12 locus May Predict Response to Piromelatine in Patients with Mild Alzheimer’s Disease (CTAD 2021) - P2 | "The 2q12 (2:107,510,000–107,540,000) 5–6 SNPs polymorphism cluster may serve as a predictor of cognitive worsening with piromelatine treatment in patients with mild Alzheimer’s disease. In line with previous reports on association between progressive cognitive deterioration with parallel deterioration in sleep (7). The main limitation in the study is the small sample due to the available GWAS specimens."

Clinical • Alzheimer's Disease • CNS Disorders • Dementia • Insomnia • Psychiatry • Schizophrenia • Sleep Disorder • APOE

Neu-P11, a novel melatonin receptor agonist, could improve the features of type-2 diabetes mellitus in rats. (PubMed, Endokrynol Pol) - "Melatonin and its receptor Neu-P11 can reduce blood glucose level, enhance humoral and cellular immunity, inhibit microglia activation and inflammation, and repair islets β cell function, improve the characterization of T2DM related diseases."

Journal • Preclinical • Diabetes • Immunology • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • CASP3 • CD86 • CDKN1A • IFNG • IL10 • IL1B • ITGAM • TNFA

Chronic Piromelatine Treatment Alleviates Anxiety, Depressive Responses and Abnormal Hypothalamic-Pituitary-Adrenal Axis Activity in Prenatally Stressed Male and Female Rats. (PubMed, Cell Mol Neurobiol) - "Piromelatine also corrected to control level the PNS-induced alterations of corticosteroid receptors only in male offspring. Our findings suggest that the piromelatine treatment exerts beneficial effects on impaired behavioral responses and dysregulated HPA axis in both sexes, while it corrects the PNS-induced changes in the hippocampal corticosteroid receptors only in male offspring."

Journal • Preclinical • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

The role of melatonin and its analogues in epilepsy. (PubMed, Rev Neurosci) - "Our search revealed several articles on the four major drugs i.e. melatonin, agomelatine, ramelteon and piromelatine along with other melatonergic agonists like tasimelteon and TIK-301. Our review is suggestive of antiseizure effects of both melatonin and its analogues; however, extensive research work is still required to study their implications in the treatment of persons with epilepsy. Further evaluation of melatonergic signaling pathways and mechanisms may prove to be helpful in the near future and might prove to be a significant advance in the field of epileptology."

Journal • CNS Disorders • Epilepsy

[VIRTUAL] Therapeutic effects of piromelatine on prenatal stress-induced emotional disturbance and hypothalamic-pituitary-adrenal axis activity in female rats (ECNP 2020) - "This drug reversed to control level the PNS-increased CORT 120 minutes after stress. Conclusion This study suggests that the novel melatoninergic drug Pir is able to alleviate anxiety and depressive responses via restoration of the impaired HPA axis feedback mechanism in PNS female offspring."

Preclinical • Alzheimer's Disease • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Anticonvulsant activity of melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, in mice. (PubMed) - Behav Brain Res - "Our study confirms the anticonvulsant potency of MLT and shows that novel synthetic MT agonists Neu-P11 and Neu-P67 have no effect on epileptic seizures in mice. Our data suggest that the activation of MT can be used in the treatment of seizures, but further pharmacological characterization is needed to understand the anticonvulsant activity of MLT and to design efficient MT-targeting antiepileptic drugs."

Journal • Biosimilar

Melatonin, but not melatonin receptor agonists Neu-P11 and Neu-P67, attenuates TNBS-induced colitis in mice. (PubMed) - Naunyn Schmiedebergs Arch Pharmacol - "Melatonin, but not MT receptor agonists, exerts potent anti-inflammatory action in acute TNBS-induced colitis. Our data suggests that melatonin attenuates colitis by additional, MT receptor-independent pathways."

Journal • Biosimilar • Immunology • Inflammatory Bowel Disease

Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION) (clinicaltrials.gov) - P2; N=500; Completed; Sponsor: Neurim Pharmaceuticals Ltd.; Active, not recruiting ➔ Completed; Trial primary completion date: Nov 2019 ➔ Jun 2019

Clinical • Trial completion • Trial primary completion date

Safety and Efficacy of Piromelatine in Mild Alzheimer's Disease Patients (ReCOGNITION) (clinicaltrials.gov) - P2; N=500; Active, not recruiting; Sponsor: Neurim Pharmaceuticals Ltd.; Trial completion date: Apr 2019 ➔ Nov 2019; Trial primary completion date: Apr 2019 ➔ Nov 2019

Clinical • Trial completion date • Trial primary completion date