Evaluation of the benefit of addition of clidinium C to a Helicobacter pylori eradication regimen

This study aimed to evaluate the success of H.pylori eradication therapy in patients with dyspepsia by therapeutics regimes with and without clidinium C. Helicobacter pylori infections are reported in all parts of the world. Appropriate antibiotic therapy can treat infection. The ideal treatment regimen has not been specified. In a randomized, double blind clinical trials study, 250 patients with dyspepsia were enrolled. All patients were treated by Omeprazole, Metronidazole, Amoxicillin and Bismuth [OMAB] for two weeks. One tablet clidinium C before each meal was added to this regimen in the intervention group [A]. Urea Breath Test [UBT] was carried out after 8-12 weeks after treatment for evaluation of H.pylori eradication. 132 patients in the intervention group [A] and 118 patients in the control group [B] were enrolled to the study. The rate of eradication in group A was significantly higher than group B [62.1% vs. 50%, p=0.04]. The results supported the effect of clidinium C for increasing of helicobacter pylori eradication, but further studies need to be performed

Spectrophotometric methods for the determination of dequalinium chloride and clidinium bromide using ion-pair complex formation with acid dyes

Dequlinium chloride is abisquaternary antiseptic, bactericidal against many gram-positive and gram negative bacteria, and effective against fungi. Clidinium bromide is a quatemary ammonium antimuscarinic with peripheral effects similar to those of atropine. It is used alone or with chlorodiazepoxide in pharmaceutical formulations for the symptomatic treatment of pepticulcer disease and other gastrointestinal disorders [1]. Spectrophotometric methods[2-11] have been reported for estimation of the two drugs in pure forms and in biological fluids. This paper describes the applicability of ion pair complexation reactions for spectra determination of [Deq] and [Clid] in pharmaceutical forms. The method involves the formation of ion-pair complexes between dequalinium chloride [Deq] and clidinium bromide [Clid] with BPB, BCG and BTB reagents. This method is applied successfully for the determination of [Deq] and [Clid] either in pure and in dosage forms, with good accuracy and precision. The results were compared with those given by the official method [12] where 1.2 gm of [Clid], accurately weighed, in 80 ml glacial acetic acid was added to 15 ml mercuric acetate and titrated with 0.1 M perchloric acid in dioxane. Each 1.0 ml of 0.1 M perchloric acid is equivalent to 43.24 mg of drug

Effects of ning shen ling granule and dehydroepiandrosterone on cognitive function in mice undergoing chronic mild stress / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the changes of spontaneous and cognitive behavior, and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS), and to determine the effect of Ning Shen Ling Granule (NSL) and dehydroepiandrosterone (DHEA) on them.</p><p><b>METHODS</b>CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources, and they were medicated for 1 week beginning at the 3rd week of modeling. The changes in behavior were determined by Morris Water Maze and spontaneous movement test, and M-receptor binding activity in cerebral cortex, hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.</p><p><b>RESULTS</b>(1) The spontaneous movement in CMS model mice was significantly reduced, with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01), and these abnormal changes in behavior were improved in those treated with NSL and DHEA. (2) The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05), but could be restored to the normal level after intervention with NSL or DHEA.</p><p><b>CONCLUSION</b>The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress, and that may be related to the low activity of central cholinergic M-receptors. Both NSL and DHEA could effectively alleviate the above-mentioned changes.</p>

Supersensitivity of the cholinergic muscarinic system in the rat's brain is induced by high concentrations of Cu+2

Transition metals have been described as regulators of receptor's function. here, we studied the effects of chronic administration of Cu2+ or the Cu2+ chelator penicillamine (PA) on the functional and binding properties of the muscarinic receptors (MR) on selected areas of rat's brain. Groups of 10 Sprague-Dawley rats were treated daily, for 45 days with either 1) 1 mg/Kg CuSO4 (Cu2+), 2) 100 mg/Kg PA, or 3) saline solution. Double T-maze and motility cages were used for behavioral testing and the binding assays were performed using [3H]-QNB or [3H]-N-MSCP as MR's ligands. Cu2+ brain levels were measured in the cerebral cortex by atomic absorption spectrophotometer. Results showed that PA treated rats displayed a significant decrease of locomotor's activity (LA) and rearing behavior (RB), but a significant increases in memory efficiency (ME). Cu2+ treated rats displayed diminished RB with no significant changes in LA. Cu2+ treated rats displayed higher MR's density (Bmax) in cortex (C), striatum (S), and hippocampus (H). An increase in Bmax was also observed in PA treated rats, but only in C and S. Finally, Cu2+ tissue concentration was significantly higher in C of both Cu2+ and with PA treated animals. In conclusion, 45 days of Cu2+ or PA treatment induced brain hypercuprosis, which was associated with MR binding supersensitivity; however, change in ME was only observed in PA treated rats suggesting that might be still another factor in these experiments besides Cu2+ (i.e., Zn2+ or PA itself) involved in memory modulation.

Cholinergic receptor activity after quinolinic acid caused cerebral injury in rats / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To provide a useful biological index for clinical diagnosis of Alzheimer's disease (AD) by determination the functional changes in the central cholinergic nerve and their effects on the peripheral lymphatic system.</p><p><b>METHODS</b>The learning and memory impairment model was established through intraventricular injecting quinolinic acid (QA) repeatedly.</p><p><b>RESULTS</b>There was a significant decline of cholineacetyltransferase (ChAT) in cerebral cortex and hippocampus after QA injection. The significantly lower binding activities of acetylcholine muscarinic (M) and nicotinic (N) cholinergic receptors in the hippocampus and cortex in the QA group were found as compared with the sham-operated group (P < 0.01). Similar changes were found in the binding activities of M-and N-receptors on spleen lymphocytes.</p><p><b>CONCLUSION</b>Certain lesion of the central nervous system can be reflected in peripheral spleen lymphocytes, which may be an important reference to diagnose the changes of the central nervous system.</p>

Multireceptor interactions of haloperidol on rat cerebral frontal cortex "in vitro"

As severall side effects of neuroleptics would be related to their interactions with several neurotransmitter receptors (R) haloperidol action on muscarinic cholinergic (mACh) R on frontal cerebral cortex preparations was analyzed. Here we shown that haloperidol was able to inhibit in a concentration dependent manner the binding of specific mAChR radiollabeled antagonist on cerebral cortex membranes. This effect would be related to its interaction on mAChR of the M1 subtype as haloperidol blocked the stimulation of phosphoiinositides (Pis) turnover induced by low concentrations of carbachol similarly as the M1 antagonist pirenzepine. However at high carbachol concentrations haloperidol triggered a potentiating stimulation of Pis hydrolysis that was only blocked by the alpha1 adrenergic antagonist prazosin indicating and alpha1 agonistic action of haloperidol on these Rs. These multireceptor actions of haloperidol found "in vitro"would strengthen its assocation with "in vivo"neuroleptic-induced side effects.

Lack of interaction of angiotensin converting enzyme inhibitors with muscarinic and neuropeptide Y receptors

In studies conducted in patients undergoing cardiac catheterizations, some hemodynamic changes were observed after the acute sublingual administration of the angiotensin converting enzyme inhibitors (ACEI) captopril, enalapril, and lisinopril. These changes consisted of an increase in pulmonary artery pressure, pulmonary vascular resistance (PVR) and induction of hypoxia. The pressure changes were transitory and disappeared after 25 min. The possible mechanisms involved in these changes may relate to interactions of the ACEI with peripheral receptor systems for hormones and neurotransmitters. We have thus undertaken the task of evaluating the potential effect of ACEI on biological receptor molecules. We have begun with studies on muscarinic receptors, and the recently characterized neuropeptide Y (NPY) receptors of endothelial cells. Equilibrium binding assays with 3H-QNB have been conducted for muscarinic receptors using rat brain synaptosomes, due to its expression of multiple muscarinic receptors subtypes. In addition 125BH-NPY binding assays were conducted on intact adrenal medullary endothelial cells. Enalapril and captopril, 10(-7) to 10(-3) M, were not able to produce significant inhibition of either muscarinic or NPY receptor probes. The paradoxical changes elicited by sublingual ACEI seems not to involve interaction with muscarinic or NPY receptors

Irritable bowel syndrome: therapeutic evaluation of indigenous drugs.

Among 169 patients with irritable bowel syndrome (IBS), standard therapy (with clidinium bromide, chlordiazepoxide and isaphaghulla), a compound Ayurvedic preparation (with Aegle marmelos correa plus Bacopa monniere Linn) along with a matching placebo were given in a double blind randomised trial for 6 wk. The Ayurvedic preparation in 57 patients was found effective in 64.9 per cent, while standard therapy (60 patients) was useful in 78.3 per cent. Patients on placebo (52 patients) showed improvement in 32.7 per cent only. Ayurvedic therapy was particularly beneficial in diarrhoea predominant form as compared to placebo. The standard therapy was more useful in the painful form of IBS as compared to placebo and Ayurvedic preparation. In gas predominant form the effect of standard as well as Ayurvedic therapy, was similar to placebo. Long-term follow-up (greater than 6 months) showed that both forms of therapy were no better than placebo in limiting the relapse.