Investigation the effect of ramelteon on urinary bladder smoth muscle contraction-relaxation mechanism

Investigation the effect of ramelteon on urinary bladder smoth muscle contraction-relaxation mechanism

Aim: A melatonin receptor agonist ramelteon is a drug that is also used in urinary tract infections. Melatonin is known to have an effect on smooth muscle contraction. In this study, we aimed to question whether ramelteon exerts a melatonin-like effect on bladder contractions. Material and Methods: Wistar-albino (n = 8) intact female rats were used in the study. After decapitation, 1.5x5 mm bladder strips were examined in an isolated organ bath in which there was Krebs-Henseleit solution. After the regulation period, ramelteon was applied non-cumulatively in two separate doses of 0.2μM, 1μM. The area under the curve (AUC) and peak to peak (p-p) values before and after the application were normalized as % change. Results: Exposure of bladder strips to ramelteon significantly increased contractions. Ramelteon caused a statistically significant increase in p-p, AUC values of spontaneous bladder contractions at a dose of 0.2 and 1μM (p < 0.05). Conclusion: Ramelteon has an activator effect on spontaneous bladder contractions unlike melatonin. The physiopathological mechanisms under activator activity need to be investigated with further studies. This effect should be taken into account in clinical use.

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  • 1. Karim A, Tolbert D, Cao C. Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia. The Journal of Clinical Pharmacology. 2006;46(2):140-8.
  • 2. Greenblatt DJ, Harmatz JS, Karim A. Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2. The Journal of Clinical Pharmacology. 2007;47(4):485-96.
  • 3. Borja NL, Daniel KL. Ramelteon for the treatment of insomnia. Clinical therapeutics. 2006;28(10):1540-55.
  • 4. Kato K, Hirai K, Nishiyama K, Uchikawa O, Fukatsu K, Ohkawa S, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology. 2005;48(2):301-10.
  • 5. McGechan A, Wellington K. Ramelteon. CNS drugs. 2005;19(12):1057-65.
  • 6. Ayar A, Kutlu S, Yilmaz B, Kelestimur H. Melatonin inhibits spontaneous and oxytocin-induced contractions of rat myometrium in vitro. Neuroendocrinology Letters. 2001;22(3):199-
  • . Harlow HJ, Weekley BL. Effect of melatonin on the force of spontaneous contractions of in vitro rat small and large intestine. Journal of pineal research. 1986;3(3):277-84.
  • 8. Matsuta Y, Yusup A, Tanase K, Ishida H, Akino H, Yokoyama O. Melatonin increases bladder capacity via GABAergic system and decreases urine volume in rats. The Journal of urology. 2010;184(1):386-91.
  • 9. Semerciöz A, Onur R, Ayar A, Orhan I. The inhibitory role of melatonin on isolated guinea-pig urinary bladder: an endogenous hormone effect. BJU international. 2004;94(9):1373-6.
  • 10. Shimizu N, Sugimoto K, Nozawa M, Kobayashi Y, Yamamoto Y, Minami T, et al. Efficacy of Ramelteon in Patients with Insomnia and Nocturia. Lower urinary tract symptoms. 2013;5(2):69-74.
  • 11. Shimizu N, Sugimoto K, Nozawa M, Kobayashi Y, Yamamoto Y, Minami T, et al. Efficacy of ramelteon in patients with insomnia and nocturia. LUTS: Lower Urinary Tract Symptoms. 2013;5(2):69-74.
  • 12. Zammit G, Wang-Weigand S, Rosenthal M, Peng X. Effect of ramelteon on middle-of-the-night balance in older adults with chronic insomnia. Journal of Clinical Sleep Medicine. 2009;5(1):34-40.
  • 13. Rauchenzauner M, Ernst F, Hintringer F, Ulmer H, Ebenbichler CF, Kasseroler MT, et al. Arrhythmias and increased neuro-endocrine stress response during physicians’ night shifts: a randomized cross-over trial. European heart journal. 2009;30(21):2606-13.
  • 14. Shimizu N, Nagai Y, Yamamoto Y, Minami T, Hayashi T, Tsuji H, et al. Survey on lower urinary tract symptoms and sleep disorders in patients treated at urology departments. Nature and science of sleep. 2013;5:7-13.
  • 15. Shimizu N, Nozawa M, Sugimoto K, Yamamoto Y, Minami T, Hayashi T, et al. Therapeutic efficacy and anti-inflammatory effect of ramelteon in patients with insomnia associated with lower urinary tract symptoms. Research and reports in urology. 2013;5:113.
  • 16. Drake M, Mills I, Noble J. Melatonin pharmacotherapy for nocturia in men with benign prostatic enlargement. The Journal of urology. 2004;171(3):1199-202.
  • 17. Sugaya K, Nishijima S, Miyazato M, Kadekawa K, Ogawa Y. Effects of melatonin and rilmazafone on nocturia in the elderly. Journal of International Medical Research. 2007;35(5):685-91.
  • 18. Nosjean O, Nicolas J-P, Klupsch F, Delagrange P, Canet E, Boutin JA. Comparative pharmacological studies of melatonin receptors: MT1, MT2 and MT3/QR2. Tissue distribution of MT3/QR2. Biochemical pharmacology. 2001;61(11):1369-79.
  • 19. Erman M, Seiden D, Zammit G, editors. Phase II study of the selective ML-1 receptor agonist TAK-375 in subjects with primary chronic insomnia. Sleep; 2003: AMER ACADEMY SLEEP MEDICINE ONE WESTBROOK CORPORATE CENTER STE 920 . . . .
  • 20. Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. The Lancet. 1995;346(8974):541-4.
  • 21. Haimov I, Lavie P, Laudon M, Herer P, Vigder C, Zisapel N. Melatonin replacement therapy of elderly insomniacs. Sleep. 1995;18(7):598-603.
  • 22. Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61(1):37-49.
  • 23. Harlow HJ, Weekley BL. Effect of melatonin on the force of spontaneous contractions of in vitro rat small and large intestine. Journal of pineal research. 1986;3(3):277-84.
  • 24. Lucchelli A, Santagostino-Barbone MG, Tonini M. Investigation into the contractile response of melatonin in the guinea-pig isolated proximal colon: the role of 5-HT4 and melatonin receptors. British journal of pharmacology. 1997;121(8):1775-81.
  • 25. Régrigny O, Delagrange P, Scalbert E, Lartaud-Idjouadiene I, Atkinson J, Chillon JM. Effects of melatonin on rat pial arteriolar diameter in vivo. British journal of pharmacology. 1999;127(7):1666-70.
  • 26. Geary GG, Duckles SP, Krause DN. Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors. British journal of pharmacology. 1998;123(8):1533-40.
  • 27. Wu L, Wang R, de Champlain J. Enhanced inhibition by melatonin of alpha-adrenoceptor-induced aortic contraction and inositol phosphate production in vascular smooth muscle cells from spontaneously hypertensive rats. Journal of hypertension. 1998;16(3):339-47.
  • 28. Ting N, Thambyraja A, Sugden D, Scalbert E, Delagrange P, Wilson V. Pharmacological studies on the inhibitory action of melatonin and putative melatonin analogues on porcine vascular smooth muscle. Naunyn-Schmiedeberg’s archives of pharmacology. 2000;361(3):327-33.
  • 29. Thor P, Krolczyk G, Gil K, Zurowski D, Nowak L. Melatonin and serotonin effects. J Physiol Pharmacol. 2007;58:97-105.
  • 30. Onur R, Ozcan M, Tuygun U, Ozan T, Ayar A, Orhan I. Effects of combined use of trospium chloride and melatonin on in vitro contractility of rat urinary bladder. Urology. 2010;75(4):873-7.
Annals of Medical Research-Cover
  • Yayın Aralığı: Aylık
  • Yayıncı: İnönü Üniversitesi Tıp Fakültesi
Sayıdaki Diğer Makaleler

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