In the present study the effects of both CCK receptor agonists and antagonists on antinociception induced by morphine in the tail-flick test have been evaluated.Morphine induced dose-dependent antinociceptionin mice. The response of morphine was potentiated by sulfated cholecystokinin-8 (CCK-8S) but not by unsulfated cholecystokinin-8 (CCK-8U). The CCK receptor antagonists MK-329 and L-365, 260 decreased the potentiation of morphine antinociception induced by CCK-8S. The antagonists even decreased the response induced by morphine in the presence of CCK-8U. High doses of MK-329 and L-365, 260 also potentiated morphine's antinociception. Single administration of the CCK receptor agonists CCK-8 and CCK-8U or CCK receptor antagonists did not elicit any response in the tail-flick test. It is concluded that CCK receptor mechanisms are involved in the modulation of pain response and/or morphine antinociception.

Background and Objectives: Opioids are an important group of analgesics that are used extensively to control sever pains. Physical dependence to these drugs is a major problem. There are a few studies regarding the involvement of cholecyctokinin (CCK) in the withdrawal syndromes of opioids. In the present study, the effects of CCK agonist and antagonist on the number of jumping of morphine dependent mice were evaluated.Materials and Methods: In this experimental study, the effects of CCK-8 and LY225910 (selective CCK2 receptor antagonist) on jumpings of mice after morphine dependence were evaluated. Mice were injected with morphine three times a day (50, 50 and 75 mg/kg) for three days; at the forth day they received 50 mg/kg morphine. Injection of naloxone (5 mg/kg) induced withdrawal signs such as jumping. The experimental groups received different doses of CCK-8 (0.1, 0.3 and 0.6 mg/kg) and LY225910 (0.01, 0.5 and 1 mg/kg) with each injection of morphine.Results: Injection of CCK-8 significantly decreased the naloxone-induced jumpings, while LY225910 did not have any significant effects on these jumpings.Conclusions: Based on the results of the present study, activation of CCK1 receptors probably is involved in morphine dependence. The results also confirm that injection of CCK but not CCK2 selective antagonist probably decreases the jumpings of mice following withdrawal syndrome of morphine.

The effects of cholecystokinin (CCK) receptor antagonists on hypothermia induced by cocaine or morphine have been studied in mice. In the present work, subcutaneous (SC) injection of cocaine (50-150 mg/kg) or morphine (125-500 mg/kg) induced hypothermia in mice. Administration of CCKA receptor antagonist MK-329 (0.5-1.5 mg/kg), CCKB receptor antagonist L-365, 260 (0.5-1.5 mg/kg) and CCK receptor antagonist proglumide (15-45 mg/kg) 60 min. prior to cocaine injection reduced hypothermia induced by cocaine. MK-329 or proglumide also reduced the morphine response. Single administration of MK-329 and L-365, 260 to mice decreased mice core body temperature. It is concluded that the hypothermic effect of cocaine and morphine may be mediated through CCKA and CCKB receptor mechanism(s).

Introduction: One of the etiological causes of nonulcer dyspepsia (NUD) is H. pylori infection. The role of H. pylori infection in dyspepsia and its accompaniment with hormonal disorders remain controversial. We studied the association between existence of H. pylori and variation of Colecystokinin (CCK) and gastrin in NUD patients.Methods: One hundred consecutive out patients with NUD that referred to Taleghani Hospital in Tehran from May 2002 to January 2003 were studied. Demographic and clinical examinations were fulfilled and basal serum gastrin and CCK level and IgG anti H. pylori were measured. After through endoscopic evaluation, gastric mucosal biopsies were taken from all patients for investigation of H. pylori (Rapid urease test (R.U.T), direct exam and IgG Anti H. pylori tests) and histological assessment.Results: 100 NUD patients including 48 (48%) male and 52(52%) female were studied. 11 patients were smoker. Fullness (62%) was the predominant symptoms in them. 59% of patients complained of abdominal pain, 57% of early satiety, 42% of anorexia, 17% of dysphagia, 46% of nausea and 20% of vomiting. 78 (78%) of patients were H. Pylori positive.In H. pylori positive group, the mean± SD of CCK was 1.06± 0.40 and gastrin was 6.68 ± 7.82. In H. pylori negative group the mean ± SD of CCK was 0.92 ± 0.31 and gastrin 8.20 ± 12.58. There was no significant difference in gastrin and CCK serum level between H. pylori positive and H. pylori negative in nonulcer dyspeptic patients. Conclusion: According to high frequency of H. pylori in NUD patients, the investigation of patients for the presence of H. pylori in patients is recommended. We didn’t find any relation between H. pylori infection and the serum level of gastrin and CCK in NUD patients.

Objectives: This study was designed to investigate the correlation between thermodynamic parameters, ideal solubility and some pharmacokinetic parameters of the compounds.Methods: For thermodynamics analysis, 5 mg of pure drug was weighed in a aluminum pan. Thermodynamic parameters were used for determination of ideal solubility. Correlation between ideal solubility and physicochemical and pharmacokinetic parameters was investigated.Results: The results indicated that there is a linear correlation between ideal solubility and permeability with R=0.8. There are also meaningful correlation between ideal solubility and other physicochemical and pharmacokinetic parameters.Conclusion: This investigation revealed that the ideal solubility could be an appropriate parameter for prediction of drugs pharmacokinetics.