Moshe Laudon

Moshe Laudon
Neurim Pharmaceuticals Ltd.

PhD

About

113
Publications
33,525
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6,218
Citations
Additional affiliations
February 1992 - November 2015
Neurim Pharmaceuticals Ltd.
Position
  • Director, Drug Discovery

Publications

Publications (113)
Article
Full-text available
The prenatal stress (PNS) model in rodents can induce different abnormal responses that replicate the pathophysiology of depression. We applied this model to evaluate the efficacy of piromelatine (Pir), a novel melatonin analog developed for the treatment of insomnia, in male and female offspring. Adult PNS rats from both sexes showed comparable di...
Article
Background: Piromelatine is a novel melatonin MT1/2/3 and serotonin 5-HT-1A/1D receptors agonist developed for mild Alzheimer's disease (AD). In a randomized, placebo-controlled, dose-ranging study (ReCognition) of piromelatine (5, 20, and 50 mg daily for 6 months) in participants with mild dementia due to AD (n=371, age 60-85 years), no statistic...
Article
Full-text available
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits, deposition of amyloid-β (Aβ) plaques, intracellular neurofibrillary tangles, and neuronal cell death. Neuroinflammation is commonly believed to participate in AD pathogenesis. CD44 is an inflammation-related gene encoding a widely-distributed f...
Article
Full-text available
Rationale Previous studies have demonstrated that piromelatine (a melatonin and serotonin 5-HT1A and 5-HT1D agonist) exerts an antidepressant activity in rodent models of acute stress and improves cognitive impairments in a rat model of Alzheimer’s disease (AD). However, the role of piromelatine in chronic stress-induced memory dysfunction remains...
Article
Full-text available
Melatonin is known as a strong antioxidant and possesses anti-inflammatory properties. Recently, melatonin was shown to improve colitis in animal models of inflammatory bowel diseases. The aim of the present study was to characterize the role of melatonin receptors (MT) in the anti-inflammatory effect of melatonin and to assess the anti-inflammator...
Article
Objective: The objective of present study was to examine the changes of melatonin receptor agonist Neu-P11 on expression of PKB and P-PKB in 3T3-L1 adipocytes and to research the variation mechanisms.Methods: 3T3-L1 pre-adipocytes were cultivated and differentiated in adipogenic cocktail by IBMX, DEX and insulin; Confirm the establishment of insuli...
Patent
Full-text available
There is provided a method of treating or preventing a neurodegenerative disease, which includes administration of a composition that includes a reagent capable of modulating expression of ribonucleic acid (RNA) encoded by a nucleic acid, wherein the nucleic acid is selected from a group that includes a contiguous nucleotide sequence being at least...
Article
Full-text available
Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. The efficacy and safety profiles of these compounds in the treatment of the indicated disorders are reviewed. Accumulating evi...
Article
Melatonin is synthesized and secreted mainly by the pineal gland in a circadian fashion, and it thus mediates endogenous circadian rhythms and influences other physiological functions. Both the G-protein coupled receptors MT1 (encoded by MTNR1A) and MT2 (encoded by MTNR1B) in mammals mediate the actions of melatonin. Evidence from vivo and vitro st...
Article
Melatonin is biosynthesized in the pineal gland and secreted into the bloodstream. Evidences indicate a role of melatonin in the regulation of glucose metabolism. The objective of this study was to investigate the effect of melatonin on insulin sensitivity in insulin resistant adipocytes. Following a preincubation with melatonin or vehicle for 30 m...
Article
Full-text available
Purpose A link between poor sleep quality and Alzheimer’s disease (AD) has recently been suggested. Since endogenous melatonin levels are already reduced at preclinical AD stages, it is important to ask whether replenishing the missing hormone would be beneficial in AD and whether any such effects would be related to the presence of sleep disorder...
Patent
Full-text available
Controlled release melatonin formulations are useful for imparting avoidance of mood depression which may be associated with administration of melatonin in conventional form comprising. Particular embodiments of methods use formulations designed to release melatonin according to a profile that simulates a normal endogenous melatonin nocturnal profi...
Article
Full-text available
An effective and safe treatment of insomnia in patients with neuropathic pain remains an unmet need. Melatonin and its analogs have been shown to have both analgesic and hypnotic effects; however, capacity of them on sleep disturbance with neuropathic pain as well as the precise mechanism is unclear. The present study evaluated effects of piromelat...
Article
Full-text available
To characterize the antinociceptive action of the novel melatonin receptor (MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. Visceral pain was induced by intracolonic (ic) application of mustard oil or capsaicin solution or by intraperitoneal (ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or ora...
Article
Chronic sleep deprivation may speed the onset or increase the severity of age-related conditions such as Type 2 diabetes, high blood pressure and obesity. Piromelatine (Neu-P11) is a novel melatonin agonist, which has been developed for the treatment of insomnia. Animal studies have suggested possible efficacy of piromelatine in sleep maintenance,...
Article
Aim: To investigate the influence of NeuP11, a novel melatonin receptor agonist, on insulin sensitivity in sleep restricted rats. Methods: Method of rotating cage was adopted to establish SD rat models of sleep restriction. During the 8 days of sleep restriction, rats were injected intraperitoneally with Neu-P11 (20 mg · kg-1)/MLT (5 mg · kg -1)/sa...
Article
Full-text available
Recently, widespread interest has grown regarding melatonin treatment of hypertension including its cardioprotective effects. Studies in rodents indicate that melatonin plays a role in the pathogenesis of hypertension in rats with metabolic syndrome. Piromelatine, a melatonin agonist, serotonin 5-HT-1A and 5-HT-1D agonist and serotonin 5-HT2B antag...
Article
Aim: To explore the possible role of adipose tissue triglyceride enzyme (ATGL) and hormone-sensitive lipase (HSL) in high glucose and insulin (HGI)-induced insulin resistance in 3T3-L1 adipocytes and the underlying mechanisms. Methods: 3T3-L1 adipocytes were administered with HGI for 24 h to induce insulin resistance. Glucose uptake and the quantit...
Article
Piromelatine, a novel investigational multimodal sleep medicine, is developed for the treatment of patients with primary and co-morbid insomnia. Piromelatine has been shown to inhibit weight gain and improve insulin sensitivity in high-fat/high-sucrose-fed (HFHS) rats. Considering that piromelatine has also been implicated in lowering of triglyceri...
Article
Full-text available
Background. Cigarette smoke is a profound proinflammatory stimulus, which causes acute lung inflammation and chronic lung disease including chronic obstructive pulmonary disease (COPD, emphysema and chronic bronchitis), via a variety of mechanisms including oxidative stress. Cigarette smoke contains high levels of free radicals, while inflammatory...
Article
Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against Aβ-induced injury in vitro and vivo. Neu-P11 (Piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptors agonist and a serotoni...
Article
Background. Cigarette smoke is a profound proinflammatory stimulus, which causes acute lung inflammation and chronic lung disease including chronic obstructive pulmonary disease (COPD, emphysema and chronic bronchitis), via a variety of mechanisms including oxidative stress. Cigarette smoke contains high levels of free radicals, while inflammatory...
Article
Introduction: Melatonin synchronizes circadian rhythms with light/dark period and it was demonstrated to correct chronodisruption. Several melatonin receptor agonists with improved pharmacokinetics or increased receptor affinity are being developed, three of them are already in clinical use. However, the actions of melatonin extend beyond chronobi...
Article
Full-text available
Patients with nocturnal hypertension are at higher risk for cardiovascular complications such as myocardial infarction and cerebrovascular insult. Published studies inconsistently reported decreases in nocturnal blood pressure with melatonin. A meta-analysis of the efficacy and safety of exogenous melatonin in ameliorating nocturnal blood pressure...
Article
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Diabetes is a major comorbidity in insomnia patients. The efficacy and safety of prolonged-release melatonin 2 mg in the treatment of glucose, lipid metabolism, and sleep was studied in 36 type 2 diabetic patients with insomnia (11 men, 25 women, age 46-77 years). In a randomized, double-blind, crossover study, the subjects were treated for 3 weeks...
Article
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Prolonged-release melatonin (PRM) 2 mg is indicated for insomnia in patients aged 55 years and older. A recent double-blind placebo-controlled study demonstrated 6-month efficacy and safety of PRM in insomnia patients aged 18-80 and lack of withdrawal and rebound symptoms upon discontinuation. To investigate the efficacy, safety, and withdrawal phe...
Article
Previous studies demonstrated the efficacy and safety of prolonged-release melatonin in children and adolescents with neurodevelopmental and behavioral disorders. The long-term effectiveness and safety of prolonged-release melatonin treatment were assessed in 88 children (42 girls and 46 boys) with neurodevelopmental disorders. These patients parti...
Article
Full-text available
The authors recently reported on efficacy and safety of prolonged-release melatonin formulation (PRM; Circadin 2  mg) in elderly insomnia patients. The age cut-off for response to PRM and the long-term maintenance of efficacy and safety were further evaluated by looking at the total cohort (age 18-80 years) from that study and subsets of patients a...
Article
Full-text available
Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term...
Article
The effects of low doses of melatonin (0.1, 0.5 and 1 mg) given at 16:00 h on induction and quality of sleep in the late afternoon (17:00-21:00 h), as well as on subjective fatigue and mood ratings before and after sleep were studied. Ten healthy male volunteers (age 26-30 years) were given on a double-blind crossover basis, tablets containing mela...
Article
Full-text available
Aim: To investigate the potential antidepressant and anxiolytic effects of Neu-P11, a novel melatonin agonist, in two models of depression in rats and a model of anxiety in mice. Methods: In the learned helplessness test (LH), Neu-P11 or melatonin (25–100 mg/kg, ip) was administered to rats 2 h before the beginning of the dark phase once a day for...
Article
Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effec...
Article
Full-text available
Melatonin, secreted nocturnally by the pineal gland, is an endogenous sleep regulator. Impaired melatonin production and complaints on poor quality of sleep are common among the elderly. Non-restorative sleep (perceived poor quality of sleep) and subsequently poor daytime functioning are increasingly recognized as a leading syndrome in the diagnost...
Article
Full-text available
Melatonin, the hormone produced nocturnally by the pineal gland, serves as a circadian time cue and sleep-anticipating signal in humans. With age, melatonin production declines and the prevalence of sleep disorders, particularly insomnia, increases. The efficacy and safety of a prolonged release melatonin formulation (PR-melatonin; Circadin* 2 mg)...
Article
Nocturnal hypertension is associated with a high risk of morbidity and mortality. A blunted nocturnal surge in melatonin excretion has been described in nondipping hypertensive patients. We therefore studied the potency of melatonin to reduce nighttime blood pressure (BP) in treated hypertensive patients with nocturnal hypertension. Thirty-eight tr...
Chapter
Study Objectives Visual analog scales (VAS) and diary cards are used to measure changes in patients’ sleep quality in clinical trials and practice. In this study we compared the 2 methods for assessing changes in sleep quality in patients with insomnia. Methods A VAS method of assessing sleep quality (QOS-means of questions 4 and 5 in the Leeds Sle...
Article
Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age-related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin thera...
Article
Melatonin, which is produced by the pineal gland at night, is an endogenous sleep regulator. Both sleep disorders and impaired melatonin production are common among the elderly. We examined the excretion of the major melatonin metabolite 6-sulfatoxymelatonin in insomnia patients aged >or=55 years and its relation with the subsequent response to mel...
Article
Full-text available
The Leeds sleep evaluation questionnaire (LSEQ) is a standardized self-reporting instrument comprising ten 100 mm visual analogue scales that pertain to the ease of getting to sleep (GTS), quality of sleep (QOS), ease of awakening from sleep (AFS) and alertness and behaviour following wakefulness (BFW). Although the LSEQ has been used in a variety...
Article
This study aimed to explore the effects of melatonin on sleep, waking up and well being in subjects with varying degrees of seasonal or weather-associated changes in mood and behaviour. Fifty-eight healthy adults exhibiting subsyndromal seasonal affective disorder (s-SAD) and/or the negative or positive type of weather-associated syndrome (WAS) wer...
Article
Melatonin plays a role in the biologic regulation of circadian rhythms, including sleep. Melatonin has also been shown to modulate vascular smooth muscle tone and to induce hemodynamic effects in humans. To evaluate whether melatonin plays a role in the circadian rhythm of blood pressure in hypertensive patients. Sixteen elderly patients with essen...
Article
The Leeds sleep evaluation questionnaire (LSEQ) comprises ten self-rating 100 mm line analogue questions concerned with sleep and early morning behaviour. A literature search identified 83 studies in peer-reviewed journals that reported the use of the LSEQ for psychopharmacological investigations of drug effects on self-reported aspects of sleep. H...
Article
The objective of this study was to investigate the effect of massage therapy on phase adjustment of rest-activity and melatonin secretion rhythms to the nocturnal period in full-term infants. Rest-activity cycles of infants (measurement 1, n = 16) were measured by actigraphy before and after 14 days of massage therapy (starting at age 10 [+/-4] d)...
Article
The preliminary applications of the psychoneuroimmunological knowledges to the treatment of human diseases have confirmed the possibility to amplify IL-2-dependent anticancer immunity by the pineal hormone melatonin (MLT) or by opioid antagonist, such as naltrexone (NTX), which act by activating TH1 lymphocytes or suppressing TH2 lymphocytes, respe...
Article
This study investigated the relationships of the excretion of the melatonin metabolite, 6-sulfatoxymelatonin, to prenatal, natal, and postnatal variables and its possible relation to psychomotor development. nocturnal urinary excretion of 6-sulfatoxymelatonin was studied over a 13-hour period in 355 term infants at 8 weeks of age (n = 320) and 16 w...
Article
Very little is known regarding melatonin's circadian rhythm in stroke patients. We compared urinary-sulfatoxymelatonin (6-SMT), its major metabolite, in 11 extensive cortical and seven deep or lacunar stroke patients on day 3 or 4 and day 10 post-stroke. Urinary 6-SMT and creatinine measured every 4 h for 24 h starting at 06:00 h significantly fluc...
Article
Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia. However, long-term treatment with antipsychotics is associated with a variety of movement disorders, the most disabling of which is tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with chronic schizophrenia. The pathophysiology of...
Article
Full-text available
With the advances in the knowledge of neuroimmunomodulation, a new era of investigations about the chemical basis of the state of mind has been initiated. Both emotions and states of spiritual consciousness may influence immune functions and cancer growth. Stress, anxiety and depressive states are associated with immunosuppression and enhanced freq...
Article
The objective of this study was to determine the normal range of nocturnal urinary excretion of the major melatonin metabolite, 6-sulfatoxymelatonin (6SMT) in a large sample of healthy full-term infants (8 and 16 wk old) and assess whether the endogenous production of melatonin changes with season. 6SMT was assessed in urine samples extracted from...
Article
The first-night effect (FNE) is the tendency for individuals to sleep worse than normal during their first night of polysomnographic sleep evaluation. FNE reflects the adaptive increase of alertness and perhaps the stress resulting from an unfamiliar sleeping environment. This effect is usually absent in patients with chronic schizophrenia. Melaton...
Article
This is the first study to examine effective doses of controlled-release (CR) melatonin in children with chronic sleep wake cycle disorders. All 42 subjects had severe neurodevelopmental difficulties. Initially, a randomized double-blinded cross-over design was used in 16 children, comparing the effectiveness of fast-release (FR) and CR melatonin....
Article
This study compares the urinary excretion of the main melatonin metabolite, 6-sulfatoxymelatonin (6SMT), in infants who have and have not experienced a life-threatening event (ALTE). 6SMT was assessed in the following groups of infants: 15 infants with ALTE for whom home monitoring had been recommended, 15 infants who had had an abrupt cyanotic apn...