Uticaj derivata žučne kiseline na analgetski efekat morfina kod miševa

  • Velibor Vasović Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Saša Vukmirović Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Momir Mikov Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Ivan Mikov Department of Occupational Medicine, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Zorana Budakov Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Nebojša Stilinović Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
  • Boris Milijašević Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia
DOI: https://doi.org/10.2298/2711
Ključne reči: morphine||, ||morfin, mice||, ||miševi, bile acids and salts||, ||žučne kiseline i soli, blood-brain barrier||, ||krvno-moždana barijera,

Sažetak


Uvod/Cilj. Poznato je da žučne kiseline poboljšavaju apsorpciju, povećavaju biološku raspoloživost i poboljšavaju farmakodinamske osobine nekih lekova. Budući da je analgezija izazvana morfinom posledica aktivacije opioidnih receptora u centralnom nervnom sistemu na spinalnom i supraspinalnom nivou, i da molekul morfina sadrži tri polarne grupe zbog čega teško prolazi kroz hematoencefalnu barijeru, cilj studije bio je da se ispita potencijalni uticaj derivata žučnih kiselina, natrijumove soli monoketoholne kiseline (MKH-Na) i metil estra monoketoholne kiseline (MKH-Me), na analgetski efekat morfina. Metode. Studija je sprovedena na belim miševima NMRI-Haan soja, muškog pola, telesne mase 20–24 g. Analgetski efekat morfina (primenjenog supkutano i intramuskularno u dozi 2 mg/kg) sa i bez pretretmana MKH-Na (4 mg/kg) i MKH-Me (4 mg/kg) procenjivan je metodom vrele ploče. Rezultati. Primena MKH-Me pre supkutane primene morfina pojačala je analgetski efekat morfina bez statistički značajne razlike. Primena MKH-Na nije uticala na analgetski efekat morfina primenjenog supkutano. Analgetski efekat intramuskularno primenjenog morfina, 20 minuta nakon primene MKH-Me, bio je pojačan. U poređenju sa grupom životinja kod kojih je primenjen samo morfin, statistički značajna razlika u analgetskom efektu zabeležena je 10, 30, 40 i 50 minuta nakon njegove  primene (p < 0,05). Pretretman sa MKH-Na nije uticao na analgetski efekat morfina primenjenog intramuskularno. Zaključak. Na osnovu rezulata studije može se pretpostaviti da nakon intramuskularne primene morfina metil estar monoketoholne kiseline povećava transport morfina u centralni nervni sistem i posledično dovodi do pojačanja analgetskog efekta morfina. Dalja istraživanja interakcija žučnih kiselina i morfina in vitro i in vivo neophodna su da bi se u potpunosti rasvetlio mehanizam interakcije, a time i mehanizam pojačanja analgetskog efekta morfina.

Biografije autora

Velibor Vasović, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, PhD, researcher

Saša Vukmirović, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, researcher

Momir Mikov, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, PhD, researcher

Ivan Mikov, Department of Occupational Medicine, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Occupational Medicine

MD, PhD, researcher

Zorana Budakov, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, researcher

Nebojša Stilinović, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, researcher

Boris Milijašević, Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Novi Sad, Serbia

Department of Pharmacology, Toxicology and Clinical Pharmacology

MD, researcher

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Objavljeno
2015/04/23
Broj časopisa
Vol. 71 Br. 8 (2014)
Rubrika
Originalni članak