Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new motilium research articles will be listed here shortly after becoming available to us.
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Medical research on motilium
Psychopharmacology (Berl). 2008 Jun 10;
Nourian Z, Mow T, Muftic D, Burek S, Pedersen ML, Matz J, Mulvany MJ
RATIONALE: Many antipsychotics cause orthostatic hypotension possibly due to antagonist action on resistance vessel alpha(1A)-adrenoceptors (alpha(1A)-AR). OBJECTIVE: We have tested this possibility by determining in Wistar rats how the orthostatic hypotensive effect of several antipsychotic drugs compares with their affinity for adrenoceptors in mesenteric small arteries (MSA with mainly alpha(1A)-AR) and aorta (mainly alpha(1D)-AR). MATERIALS AND METHODS: Using a tilt setup, orthostatic hypotension was measured in anaesthetized rats for prazosin and the antipsychotics haloperidol, sertindole, risperidone, clozapine, ziprasidone, domperidone, olanzapine, and aripiprazole. For in vitro studies, segments of MSA and aorta were mounted on a wire myograph for isometric tension recording. Cumulative concentration-response curves were constructed to phenylephrine (PE) in the absence and presence of the drugs. Apparent affinity (pA (2)) was calculated by Schild analysis. RESULTS: Prazosin antagonized tilt-induced and PE responses in both studies (threshold 4 ng/ml, pA (2) 9.52 MSA, 10.1 aorta). The rank order of the potency of the antipsychotics in the tilt experiments correlated (r (2) = 0.69, P = 0.01) with the pA (2)-values in MSA: Risperidone and sertindole had the highest potency in the tilt test (threshold 159 and 97 ng/ml) and the highest apparent affinity in MSA (pA ( 2 ) 8.92 and 8.78), in contrast with aripiprazole and domperidone, which had the lowest in each case (threshold 4.1 and 3.0 mug/ml, pA (2) 7.17 and 6.99). In aorta, the pA (2) values did not correlate with the in vivo potencies; in particular, sertindole had no functional affinity in aorta. CONCLUSION: We conclude that the orthostatic hypotensive effect in rats of the antipsychotic drugs investigated is mediated through alpha(1A)-ARs.
Domperidone and sudden death. Cardiac rhythm disorders: QT interval prolongation.
Prescrire Int. 2008 Apr; 17(94): 67
[Effects of Tangweian granule on 5-HT(2A)R in rat model with diabetic gastroparesis]
Zhongguo Zhong Yao Za Zhi. 2008 Mar; 33(5): 541-4
Qian QH, Wang ZC, Zhao Y, Liu DW, Qian WB
OBJECTIVE: To observe the effects of Tangweian granule on 5-HT(2A)R in rat model with diabetic gastroparesis (DGP). METHOD: The rats with diabetic gastroparesis induced by injecting alloxan and giving 200% Radix Rehmanniae preparata were divided into four groups randomly: Tangweian high dosage group, Tangweian low dosage group, motilium control group and the model control group, 10 rats each group. Each group was irrigated with drugs during establishing the model. Additionally, we chose 10 rats by way of normal control group. Further more, Tangweian high dosage group were irrigated stomach with gliclazide 20 mg x kg(-1) and Tangweian granule 31.75 g x kg(-1); Tangweian low dosage group were irrigated stomach with gliclazide 20 mg x kg(-1) and Tangweian granule 15.88 g x kg(-1); motilium control group were irrigated stomach with gliclazide 20 mg x kg(-1) and motilium 3.75 mg x kg(-1) and the model control group were irrigated stomach with distilled water. Then the effects of Tangweian granule on 5-HT(2A)R were observed. RESULT: The curative group had better effects than the control group in lowering the blood sugar and the level of 5-HT(2A)R content (P < 0.01). And there was significant difference between the curative group and control group (P < 0.05). CONCLUSION: It is verified that Tangweian granule has obvious effects on lowering the blood sugar and improving the level of 5-HT(2A)R.
A Systematic Review of the Efficacy of Domperidone for the Treatment of Diabetic Gastroparesis.
Clin Gastroenterol Hepatol. 2008 Jun 2;
Sugumar A, Singh A, Pasricha PJ
BACKGROUND & AIMS: Despite being widely used in more than 20 countries for the treatment of diabetic gastroparesis for several decades, domperidone is approved only on an investigational basis in the United States. However, because its use is increasing, it is important for gastroenterologists in this country to understand its effectiveness in this condition. The literature on this subject varies considerably with respect to the methods and outcome measures, making a meta-analysis unfeasible. METHODS: Our objective was to systematically analyze studies of the efficacy of domperidone in diabetic gastroparesis, with a focus on their methodologic and scientific merit. Information from 28 trials (11 full articles and 17 abstracts) from 1981 to 2007 was analyzed. RESULTS: The average study quality score was 8.3 out of a possible 15 and the total sample size equaled 1016. Overall, 64% of the studies showed significant efficacy of domperidone on the improvement of symptoms. Sixty percent of the studies showed an efficacy in gastric emptying and 67% of the studies proved the drug effective in reducing hospital admissions. CONCLUSIONS: Overall, our assessment is that there is level 3 evidence for the efficacy of domperidone in diabetic gastroparesis, leading to a grade C recommendation for its use in this condition. These results need to be interpreted very cautiously because of significant methodologic limitations of these studies, including the fact that most positive studies lacked a control arm. It is clear that larger and better-designed studies are needed to further validate the use of this drug in diabetic gastroparesis.
Gastric floating matrix tablets: Design and optimization using combination of polymers.
Acta Pharm. 2008 Jun 1; 58(2): 223-231
Prajapati ST, Patel LD, Patel DM
The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.
Am J Physiol Regul Integr Comp Physiol. 2008 May 28;
Soliz J, Soulage C, Borter E, Tissot van Patot MC, Gassmann M
Proteins harboring a Per-Arnt-Sim (PAS) domain are versatile and allow archaea, bacteria and plants to sense oxygen partial pressure as well as light intensity and redox potential. A PAS domain associated with a histidine kinase domain is found in FixL, the oxygen sensor molecule of Rhizobium species. Considering the PAS fold PASKIN is the mammalian homolog of FixL, but its function is far from being understood. Using whole body plethysmography we evaluated the ventilatory response to acute and chronic hypoxia of homozygous deficient male and female PASKIN mice (Paskin(-/-)). While only slight ventilatory differences were found in males, female Paskin(-/-) mice increased ventilatory response to acute hypoxia. Unexpectedly, females had an impaired ability to reach ventilatory acclimatization in response to chronic hypoxia. Central control of ventilation occurs in the brainstem respiratory centers and is modulated by catecholamines via tyrosine hydroxylase (TH) activity. We observed that TH activity was altered in male and female Paskin(-/-) mice. Peripheral chemoreceptor effects on ventilation were evaluated by exposing animals to hyperoxia (Dejours test) and domperidone, a peripheral ventilatory stimulant drug directly affecting the carotid sinus nerve discharge. Male and female Paskin(-/-) had normal peripheral chemosensory (carotid bodies) responses. In summary, our observations suggest that PASKIN is involved in the central control of hypoxic ventilation, modulating ventilation in a gender-dependent manner. Key words: Ventilatory control, hypoxia, gender differences, oxygen sensing, carotid bodies.
Br J Clin Pharmacol. 2008 May 26;
Wan EW, Davey K, Page-Sharp M, Hartmann PE, Simmer K, Ilett KF
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT * Domperidone is an effective treatment for some mothers with insufficient milk supply. * However, dose-effect data are not available, and the safety of domperidone use in both mother and infant has been questioned. WHAT THIS STUDY ADDS * Domperidone only increases milk production in about two-thirds of preterm mothers with insufficient milk supply. * On average, the responders showed increasing levels of milk production with dose escalation from 30 mg to 60 mg daily. * The amount of domperidone that transferred into breast milk was very low, and the risk to the breastfed infant is minimal. AIMS To investigate the possibility of a dose-response relationship for the use of domperidone in treating insufficient milk supply in mothers of preterm infants, and to quantify the exposure of the breastfed infant to domperidone. METHODS Six preterm mothers received domperidone (30 mg daily or 60 mg daily) in a double-blind, randomized, crossover trial. Milk production and serum prolactin were measured before and during the trial, and domperidone concentration in milk was measured during drug treatment. RESULTS For milk production, two of the mothers were 'nonresponders', whereas the other four were 'responders' and showed a significant increase in milk production from 8.7 +/- 3.1 g h(-1) in the run-in phase (mean +/- SEM), 23.6 +/- 3.9 g h(-1) for the 30-mg dose (P = 0.0217) and 29.4 +/- 6.6 g h(-1) for the 60-mg dose (P = 0.0047). In all participants, serum prolactin was significantly increased for both doses, but the response was not dose dependent. Median (interquartile range) domperidone concentrations in milk over a dose interval at steady-state were 0.28 microg l(-1) (0.24-0.43) and 0.49 microg l(-1) (0.33-0.72) for the 30-mg and 60-mg doses, respectively. The mean relative infant dose was 0.012% at 30 mg daily and 0.009% at 60 mg daily. CONCLUSION In one-third of mothers, domperidone did not increase milk production. In the remainder, milk production increased at both domperidone doses, and there was a trend for a dose-response relationship. The amount of domperidone that transfers into milk was extremely low, and infant exposure via breastfeeding was not considered to be significant.
Clin Exp Pharmacol Physiol. 2008 May 23;
Eliassi A, Aleali F, Ghasemi T
1. It has been documented that dopamine, an important regulator of gastric function in the brain-gut axis, has an inhibitory effect on the gastric acid secretion. It has also been suggested that dopamine D1, D2 and D5 receptor proteins are present in the gastrointestinal tract from the stomach through to the distal colon. Therefore, we hypothesized that peripheral D2 receptors may be involved in the control of stimulated gastric acid secretion. To address this question, we examined the effect of quinpirole, a selective D2 receptor-like agonist, and domperidone, a peripheral D2 receptor antagonist, on rat gastric acid secretion. 2. Quinpirole (0.0001-0.5 mg/kg, i.p.) was administered simultaneously with intravenous infusions of histamine, pentagastrin, and carbachol. In some experiments, domperidone (3 and 7 mg/kg) was administered 30 min before quinpirole injection. 3. We found that intraperitoneal injection of quinpirole (0.0001-0.5 mg/kg) suppressed stimulated gastric acid secretion induced by histamine (0.08 mg/100 g per h), pentagastrin (1 microg/100 g per h) and carbachol (4 microg/100 g per h) in a dose-dependent manner. This inhibitory effect of quinpirole persisted until the end of the experiments (90-120 min) and was completely suppressed by domperidone (7 mg/kg). 4. In conclusion, the results of the present study suggest that peripheral D2-like receptors have an inhibitory effect on histaminergic-, pentagastrin- and cholinergic-stimulated gastric acid secretion. This inhibitory effect may be mediated by enteric dopaminergic neurons and/or non-neuronal membranes.
J AOAC Int. 2008 Mar-Apr; 91(2): 344-8
Sabnis SS, Dnvandev DN, Jadhav VY, Gandhi SV
A new, simple column reversed-phase high-performance liquid chromatographic (HPLC) method for simultaneous determination of rabeprazole sodium (RAB) and domperidone (DOM) in a combined tablet dosage form has been developed and validated. Determination was performed using a Jasco HPLC system with a HiQ SiL octadecylsilane (C18) column (250 x 4.6 mm id), acetonitrile-0.1 M ammonium acetate (50 + 50, v/v) mobile phase, and paracetamol as an internal standard. The detection was performed using a UV detector set at 280 nm. The method was validated with respect to linearity, accuracy, precision, and robustness. Beer's law was obeyed in the concentration range of 1.0-10.0 and 0.5-5.0 microg/mL for RAB and DOM, respectively. The method has been successfully applied for the analysis of drugs in a pharmaceutical formulation.
Forty cases of gastrointestinal neurosis treated by acupunture.
J Tradit Chin Med. 2008 Mar; 28(1): 15-7
Zhao Y, Ding M, Wang Y
OBJECTIVE: To compare the therapeutic effect of acupuncture for gastrointestinal neurosis with that of oral remedy. METHODS: Eighty cases were randomly divided into the following 2 groups. In the treatment group, acupuncture was given for one month at the main points of Zhongwan (CV 12), Zusanli (ST 36), Taichong (LR 3) and Shenmen (HT 7), with the auxiliary points selected according to TCM differentiation. In the control group, Domperidone was orally administered for one month. RESULTS: The total effective rate was 92.5% in the treatment group and 75.0% in the control group, with a significant difference between the 2 groups (chi2 = 4.423, P < 0.05). Acupuncture was superior to the oral remedy in therapeutic effects. CONCLUSIONS: Acupuncture may show better results for gastrointestinal neurosis and with less toxic side effects.