Neurim Pharmaceuticals is a drug discovery and development company. Circadin® – a prolonged release melatonin for insomnia is the first Rx to be approved in 2007 for the Insomnia disease.

 
 
  TEVA, LUNDBECK, NYCOMED
 
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Insomnia
 
Parkinson’s disease
 
Asthma/COPD
 
 
 
 
 
  1. Haimov, I., Laudon, M., Zisapel, N., Souroujon, M., Nof, D., Schlitner, A.,and Lavie, P. The relationship between urinary 6 sulfatoxy melatonin rhythm and insomnia in old age. Adv. Pin. Res. 8: 433-438 (1994).
  2. Haimov, I., Laudon, M., Zisapel, N., Souroujon, M., Nof, D., Schlitner, A., Herer, P., Tzischinsky, O. and Lavie, P. Sleep disorders and melatonin rhythms in elderly people. Brit. Med. J. 309: 167-168 (1994).
  3. Haimov, I., Lavie, P. , Laudon, M., Herer, P., Vigder, C. and Zisapel, N.Melatonin replacement therapy of elderly insomniacs. Sleep 18: 598-603 (1995).
  4. Garfinkel, D., Laudon, M., Nof, D. and Zisapel, N. Improvement of sleep quality in elderly people by controlled release melatonin. The Lancet 364: 541-544 (1995).
  5. Laudon, M., Gilad, E., Matzkin, H., Braf, Z. and Zisapel, N. Putative melatonin receptors in benign human prostate tissue. J. Clin Endocrinol. Metab. 81:1336-1342 (1996).
  6. Gilad, E., Laudon, M., Matzkin, H. Pick, Sofer, M., Braf, Z. and Zisapel, N. Functional melatonin receptors in human prostate epithelial cells. Endocrinology 137;1412-1417 (1996).
  7. Atsmon, J., Oaknin-Bend, S., Laudon, M., Laschiner, S., Gavish, M. Dagan, Y. and Zisapel, N. Reciprocal effects of chronic diazepam and melatonin on brain melatonin and benzodiazepine binding sites. J. pineal Res. 20: 65-71 (1996).
  8. Garfinkel, D. and Zisapel, N. Liver cirrhosis and circadian rhythms. Annals Int. Med. 125:154 (1996).
  9. Laudon, M. Tarasch R. and Zisapel N. Effects of fast and slow release melatonin formulations on daytime sleep and mood. in: Pineal update-from molecular mechanisms to clinical implications (SM Webb, M Puig-Domingo, M. Moller and P Pevet eds) PJD Publicatons NY (1997).
  10. Garfinkel, D., Laudon, M. and Zisapel, N. Improvement of sleep quality by controlled-release melatonin in benzodiazepine treated elderly insomniacs. Arch. Gerontol. Geriat. 24:223-231 (1997).
  11. Terlo, L., Laudon, M., Tarasch, R., Schatz, T., Caine, Y.G. and Zisapel N. Effects of low doses of melatonin on late afternoon napping and mood . Biol. Rhythm. Res. 28:2-16 (1997).
  12. Dagan, Y., Zisapel, N., Nof, D., Laudon, M. and Atsmon, J. Rapid reversal of tolerance to benzodiazepine hypnotics by treatment with oral melatonin: a case report. Eur. Neuropsychpharmacol. 7:157-160 (1997).
  13. Zisapel, N. and Garfinkel, D. Use of controlled release melatonin for insomnia in older persons. Clinical Geriatrics 5:17-27 (1997).
  14. Garfinkel D and Zisapel, N. The use of melatonin for sleep. Nutrition (editorial) 14:53-55 (1998).
  15. Bubenik, GA, Blask, DE, Brown, GM, Maestroni, GJ, Pang, SF, Reiter, RJ, Viswanathan M Zisapel, N. Prospects of the clinical utilization of melatonin Biol Signals Recept 7;195-219 (1998).
  16. Laudon M and Zisapel N Melatonin deficiency and its implications for the treatment of insomnia in elderly subjects The Aging Male 1:244-253 (1998).
  17. Zisapel, N. The use of melatonin in the treatment of insomnia. Biol Signals Recept. 8:84-89 (1999).
  18. Garfinkel, D., Zisapel, N. and Laudon, M. Facilitation of benzodiazepine discontinuation by melatonin- a novel clinical use. Arch. Int. Med 159:2456-2460 (1999).
  19. Zisapel, N. Development of a melatonin based formulation for the treatment of insomnia. Drug Dev Res 50:226-234 (2000).
  20. Shamir, E., Laudon, M., Barak, Y., Anis, Y., Rotenberg, V., Elizur, A. and Zisapel N. Melatonin improves sleep quality of chronic schizophrenic patients. Journal Clin. Psychiatry 61:373-378 (2000).
  21. Sivan, Y. Laudon, M., Kuint, J. and Zisapel N. Low melatonin production in infants with a life threatening event. Dev Med Child Neurol 42: 487-491(2000).
  22. Shamir, E., Laudon, M., Barak, Y., Anis, Y., Rotenberg, V., Elizur, A. and Zisapel N. First night effect under melatonin treatment of patients with chronic schizophrenia J. Clin Psychopharmacol 20:691-694 (2000).
  23. Shamir E, Barak Y, Plopsky I, Zisapel N, Elizur A , and Weizman A. Is melatonin treatment effective in tardive ? dyskinesia? J Clin Psychiat 61:556-558 (2000).
  24. Zisapel, N. Circadian Rhythm Sleep Disorders: Pathophysiology and Potential Approaches to Management CNS Drugs 15:311-328 (2001).
  25. Sivan, J., Laudon, M., Tauman, R., and Zisapel, N. Melatonin production in healthy infants:Evidence for seasonal variations Pediatric Res 49:63-68 (2001)
  26. Shamir E, Barak Y, Shalman I, Laudon M, Zisapel N, Tarrasch R, Elizur A and Weizman R. Melatonin treatment for tardive - dyskinesia:A double-blind placebo-controlled cross-over study 58:1049-1052 (2001).
  27. Zisapel N. Melatonin-Dopamine Interactions: From Basic Neurochemistry to a Clinical Setting Molec Cell Neurobiol. 21:605-616 (2001).
  28. Beloosesky Y, Grinblat J, Laudon M, Grosman B, Streifler JY and Zisapel N. Melatonin rhythms in stroke patients Neurosci Lett 319:103-6 (2002).
  29. Tauman, R., Zisapel, N., Laudon, M., Nehama, H and Sivan, Y. melatonin production in infants: association with perinatal and postnatal factors. Pediat. Neurol. 26:379-82 (2002).
  30. Zisapel N and Laudon M. Subjective Assessment of the Effects of CNS-Active Drugs on Sleep by The Leeds Sleep Evaluation Questionnaire: A Review Human Neuropsychopharmacology: clinical & experimental 18:1-20 (2003).
  31. Jonas M, Garfinkel, D., Zisapel, N., Laudon, M. and Grossman E.Impaired Nocturnal melatonin Secretion in non-dipper hypertensive patients Blood pressure 12:1-6 (2003).
  32. Leppamaki S, Partonen T, Vakkuri O, Lonngvist J, Partinen M, Laudon M. Effect of controlled-release melatonin on slepp quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour. Eur Neuropsychopharmacol. 12:137-45 (2003).
  33. Tarrasch R, Laudon M, Zisapel N. Cross-cultural validation of the Leeds sleep evaluation questionnaire (LSEQ) in insomnia patients. Hum Psychopharmacol. 18:603-10 (2003).
  34. Zisapel N, Nir T. Determination of the minimal clinically significant difference on a patient visual analog sleep quality scale. Sleep Res. 12:291-8 (2003).
  35. Leger D, Laudon M, Zisapen N. Nocturnal 6-sulfatoxymelatonin excretion in insomnia and its relation to the response to melatonin replacement therapy. Am J Med. 116:91-5 (2004).
  36. Pandi-Perumal SR, Zisapel N, Srinivasan V, Cardinali DP. Melatonin and sleep in aging population. Exp Gerontol. 40:911-25 (2005).
  37. Grossman E, Laudon M, Yalcin R, Zengil H, Peleg E, Sharabi Y, Kamari Y, Shen-Orr Z, Zisapel N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med. 119:898-902 (2006).
  38. Gorfine T, Assaf Y, Goshen-Gottstein Y, Yeshurun Y, Zisapel N. Sleep-anticipating effects of melatonin in the human brain. Neuroimage. 31:410-8 (2006).
  39. Gorfine T, Zisapel N. Melatonin and the human hippocampus, a time dependent interplay.J Pineal Res. ;43:80-6 (2007).
  40. Zisapel N. Sleep and sleep disturbances: biological basis and clinical implications. Cell Mol Life Sci. (2007).
  41.  Wade A, Ford , Crawford, G, McMahon AD, Nir T, Laudon M and Zisapel N. Efficacy of prolonged release melatonin in insomnia patients aged 55–80 years: quality of sleep and next-day alertness outcomes. Current Medical Research and Opinion. 23: 2597–2605 (2007).
  42. Gorfine T, Yeshurun Y, Zisapel N. Nap and melatonin-induced changes in hippocampal activation and their role in verbal memory consolidation. J Pineal Res.;43:336-42 (2007).
  43. Lemoine P, Nir T, Laudon M and Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J. Sleep Res. 16:372-380 (2007)
  44. Luthringer R, Muzet M, Zisapel N, Staner L. The effect of prolonged-release melatonin on sleep measures and psychomotor performance in elderly patients with insomnia(corrected). Int Clin Psychopharmacol 2009 Sep;24(5):239-49.
  45. Otmani S, Demazieres A, Staner C, et al. Effects of prolonged-release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers. Hum Psychopharmacol 2008;23(8):693-705
  46. Wade A, Zisapel N, Lemoine P. Prolonged-release melatonin for the treatment of Insomnia: targeting quality of sleep and morning alertness. Aging Health 2008;1:11-21.
  47. Zisapel N, Lemoine P. Efficacy and Safety of Circadin® in the Treatment of Primary Insomnia. TOUCHBRIEFINGS 2008 .