Latest medical literature on bentyl

Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new bentyl research articles will be listed here shortly after becoming available to us.

Medical research on bentyl

Interaction between glutamatergic-NMDA and cholinergic-muscarinic systems in classical fear conditioning.

Brain Res Bull. 2008 Jun 23;
Figueredo LZ, Moreira KD, Ferreira TL, Fornari RV, de Oliveira MG
A number of studies have suggested that the glutamatergic and cholinergic systems are both involved in learning and memory processes and that they interact in order to facilitate these processes. However, the role of M1-muscarinic receptors in mediating this interaction has not been elucidated. The aim of this study was to determine whether the concomitant administration of MK-801 (non-competitive NMDA antagonist) and dicyclomine (M1-muscarinic antagonist - DIC) in sub-effective doses impairs contextual fear conditioning (hippocampal-dependent task) and tone fear conditioning tasks (hippocampal-independent task). The results showed that concomitant pre-training administration of DIC (8.0mg/kg) and MK-801 (0.07mg/kg) - two sub-effectives doses for the contextual fear conditioning task - does impair the performance of animals on this task (as measured by freezing behavior time). Tone fear conditioning tasks were not affected by the drugs either administered separately or concurrently. The pre-training administration of sub-effective doses of MK-801 and DIC in combination impairs performance on contextual fear conditioning task (hippocampal-dependent), but not on tone fear conditioning task (hippocampal-independent). These data support the hypothesis that the interaction between glutamatergic and cholinergic systems in hippocampus-dependent learning and memory processes probably occurs through M1 receptor.

Anticholinergic Activity of 107 Medications Commonly Used by Older Adults.

J Am Geriatr Soc. 2008 May 26;
Chew ML, Mulsant BH, Pollock BG, Lehman ME, Greenspan A, Mahmoud RA, Kirshner MA, Sorisio DA, Bies RR, Gharabawi G
The objective of this study was to measure the anticholinergic activity (AA) of medications commonly used by older adults. A radioreceptor assay was used to investigate the AA of 107 medications. Six clinically relevant concentrations were assessed for each medication. Rodent forebrain and striatum homogenate was used with tritiated quinuclidinyl benzilate. Drug-free serum was added to medication and atropine standard-curve samples. For medications that showed detectable AA, average steady-state peak plasma and serum concentrations (C(max)) in older adults were used to estimate relationships between in vitro dose and AA. All results are reported in pmol/mL of atropine equivalents. At typical doses administered to older adults, amitriptyline, atropine, clozapine, dicyclomine, doxepin, L-hyoscyamine, thioridazine, and tolterodine demonstrated AA exceeding 15 pmol/mL. Chlorpromazine, diphenhydramine, nortriptyline, olanzapine, oxybutynin, and paroxetine had AA values of 5 to 15 pmol/mL. Citalopram, escitalopram, fluoxetine, lithium, mirtazapine, quetiapine, ranitidine, and temazepam had values less than 5 pmol/mL. Amoxicillin, celecoxib, cephalexin, diazepam, digoxin, diphenoxylate, donepezil, duloxetine, fentanyl, furosemide, hydrocodone, lansoprazole, levofloxacin, metformin, phenytoin, propoxyphene, and topiramate demonstrated AA only at the highest concentrations tested (patients with above-average C(max) values, who receive higher doses, or are frail may show AA). The remainder of the medications investigated did not demonstrate any AA at the concentrations examined. Psychotropic medications were particularly likely to demonstrate AA. Each of the drug classifications investigated (e.g., antipsychotic, cardiovascular) had at least one medication that demonstrated AA at therapeutic doses. Clinicians can use this information when choosing between equally efficacious medications, as well as in assessing overall anticholinergic burden.

Antagonism of muscarinic M1 receptors by dicyclomine inhibits the consolidation of morphine-associated contextual memory.

Brain Res Bull. 2008 Jul 1; 76(4): 380-7
Esmaeili B, Basseda Z, Dehpour AR
M1 muscarinic receptor has been shown to be involved in cognitive functions of the brain. Conditioned place preference (CPP) paradigm involves memory for the association between environmental stimuli and the rewarding properties produced by a treatment. Using a balanced CPP design, we studied the possible involvement of M1 muscarinic receptors on the acquisition, expression and consolidation of morphine place conditioning in male mice. Subcutaneous administration of morphine sulphate-induced CPP in a dose-dependent manner. Using a 6-day schedule of conditioning, it was found that dicyclomine, an M1 muscarinic antagonist, significantly reduced the time spent by mice in the morphine compartment when given immediately, but not 6h, after each conditioning session (consolidation). It had no effect when administered 30 min before each conditioning session during CPP training period (acquisition) or 30 min before testing for place preference in the absence of morphine (expression). It is concluded that M1 muscarinic receptors may play a time-dependent role in the consolidation of reward-related memory of morphine.

Blockade of M1 muscarinic acetylcholine receptors modulates the methamphetamine-induced psychomotor stimulant effect.

Neuroscience. 2008 Jun 2; 153(4): 1235-44
Lee KW, Tian YH, You IJ, Kwon SH, Ha RR, Lee SY, Kim HC, Jang CG
Muscarinic acetylcholine receptors (M1-M5) regulate many key functions of the CNS and peripheral nervous system. In the present study, the role of M1 muscarinic receptors (M1R) in the psychomotor stimulant and sensitizing properties of methamphetamine (METH) is investigated using molecular, neurochemical, and behavioral approaches. Acute and repeated treatment with METH increased M1R mRNA expression in the frontal cortex and the CA2 region of the hippocampus. Repeated treatment with METH also increased M1R mRNA expression in the dentate gyrus. Dicyclomine, an M1R antagonist, did not affect the psychomotor effect of METH, but it attenuated METH-induced increases in the dopamine (DA) efflux in the nucleus accumbens (NAc). Dicyclomine enhanced the psychomotor effect of METH after repeated treatment with METH and 8.0 mg/kg of dicyclomine, and also augmented the increase in the NAc DA overflow evoked by repeated METH treatment. These results suggest that M1R plays a role in the METH-induced psychomotor stimulant effect by changing the release of DA in the NAc of mice.

Mechanisms underlying the antispasmodic and bronchodilatory properties of Terminalia bellerica fruit.

J Ethnopharmacol. 2008 Mar 28; 116(3): 528-38
Gilani AH, Khan AU, Ali T, Ajmal S
AIM OF THE STUDY: The present investigation was carried out to provide the pharmacological basis for the medicinal use of Terminalia bellerica in hyperactive gastrointestinal and respiratory disorders. MATERIALS AND METHODS: Crude extract of Terminalia bellerica fruit (Tb.Cr) was studied in in vitro and in vivo. RESULTS: Tb.Cr caused relaxation of spontaneous contractions in isolated rabbit jejunum at 0.1-3.0mg/mL. Tb.Cr inhibited the carbachol (CCh, 1microM) and K(+) (80mM)-induced contractions in a pattern similar to that of dicyclomine, but different from nifedipine and atropine. Tb.Cr shifted the Ca(++) concentration-response curves to right, like nifedipine and dicyclomine. In guinea-pig ileum, Tb.Cr produced rightward parallel shift of acetylcholine-curves, followed by non-parallel shift at higher concentration with the suppression of maximum response, similar to dicyclomine, but different from nifedipine and atropine. Tb.Cr exhibited protective effect against castor oil-induced diarrhea and carbachol-mediated bronchoconstriction in rodents. In guinea-pig trachea, Tb.Cr relaxed the CCh-induced contractions, shifted CCh-curves to right and inhibited the contractions of K(+). Anticholinergic effect was distributed both in organic and aqueous fractions, while CCB was present in the aqueous fraction. CONCLUSIONS: These results indicate that Terminalia bellerica fruit possess a combination of anticholinergic and Ca(++) antagonist effects, which explain its folkloric use in the colic, diarrhea and asthma.

Gastrointestinal, selective airways and urinary bladder relaxant effects of Hyoscyamus niger are mediated through dual blockade of muscarinic receptors and Ca2+ channels.

Fundam Clin Pharmacol. 2008 Feb; 22(1): 87-99
Gilani AH, Khan AU, Raoof M, Ghayur MN, Siddiqui BS, Vohra W, Begum S
This study describes the spasmolytic, antidiarrhoeal, antisecretory, bronchodilatory and urinary bladder relaxant properties of Hyoscyamus niger to rationalize some of its medicinal uses. The crude extract of H. niger seeds (Hn.Cr) caused a complete concentration-dependent relaxation of spontaneous contractions of rabbit jejunum, similar to that caused by verapamil, whereas atropine produced partial inhibition. Hn.Cr inhibited contractions induced by carbachol (1 microM) and K(+) (80 mM) in a pattern similar to that of dicyclomine, but different from verapamil and atropine. Hn.Cr shifted the Ca(2+) concentration-response curves to the right, similar to that caused by verapamil and dicyclomine, suggesting a Ca(2+) channel-blocking mechanism in addition to an anticholinergic effect. In the guinea-pig ileum, Hn.Cr produced a rightward parallel shift of the acetylcholine curves, followed by a non-parallel shift with suppression of the maximum response at a higher concentration, similar to that caused by dicyclomine, but different from that of verapamil and atropine. Hn.Cr exhibited antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation in mice. In guinea-pig trachea and rabbit urinary bladder tissues, Hn.Cr caused relaxation of carbachol (1 microM) and K(+) (80 mM) induced contractions at around 10 and 25 times lower concentrations than in gut, respectively, and shifted carbachol curves to the right. Only the organic fractions of the extract had a Ca(2+) antagonist effect, whereas both organic and aqueous fractions had anticholinergic effect. A constituent, beta-sitosterol exhibited Ca(2+) channel-blocking action. These results suggest that the antispasmodic effect of H. niger is mediated through a combination of anticholinergic and Ca(2+) antagonist mechanisms. The relaxant effects of Hn.Cr occur at much lower concentrations in the trachea and bladder. This study offers explanations for the medicinal use of H. niger in treating gastrointestinal and respiratory disorders and bladder hyperactivity.

Improving the detection limits of antispasmodic drugs electrodes by using modified membrane sensors with inner solid contact.

J Pharm Biomed Anal. 2007 May 9; 44(1): 8-15
Ibrahim H, Issa YM, Abu-Shawish HM
Three coated wire electrodes (CWEs) for the antispasmodic drugs; dicyclomine (Dc), mebeverine (Mv) and drotaverine (Dv) hydrochlorides were developed. Each electrode based on ion-associate of a heteropoly anion with the drug cation incorporated in membrane sensor modified with graphite and deposited on silver internal solid contact. The influence of addition of graphite to the membranes and the type of the internal solid contact on the potentiometric responses of the electrodes was investigated. The characteristics of the new electrodes were compared to the characteristics of previously reported traditional liquid inner contact electrodes of the same drugs. The lower detection limits of the proposed electrodes were somewhat better than those observed with the corresponding liquid contact ISEs and reached (1.2-2.0)x10(-7)M. The potentiometric selectivity of the CWEs revealed a significant improvement and much faster response times compared to the liquid contact ISEs. The practical utility of each electrode has been demonstrated by using it successfully in potentiometric determination of its respective drug in pharmaceutical preparations both in batch and flow injection conditions. Each electrode was also used as an indicator electrode in the potentiometric titration of the drug against standard silicotungstic acid and in potentiometric determination of the drug concentration in urine samples.

[Drug treatment of irritable bowel syndrome: an unmet need]

Gastroenterol Hepatol. 2007 Mar; 30(3): 130-7
Mearin F

Current gut-directed therapies for irritable bowel syndrome.

Curr Treat Options Gastroenterol. 2006 Jul; 9(4): 314-23
Chang HY, Kelly EC, Lembo AJ
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT(4) agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC(2) chloride channel opener lubiprostone, mu-opioid receptor antagonist alvimopan, and 5-HT(4) agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT(3) antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.

Clinical inquiries. What is the best treatment for infants with colic?

J Fam Pract. 2006 Jul; 55(7): 634-6
Crotteau CA, Wright ST, Eglash A
Infantile colic, defined as excessive crying in an otherwise healthy baby, is a distressing phenomenon, but there is little evidence to support the many treatments offered. Several small studies report some benefit from use of a hypoallergenic (protein hydrolysate) formula, maternal diet adjustment (focusing on a low-allergen diet), and reduced stimulation of the infant. While dicyclomine has been shown to be effective for colic, there are significant concerns about its safety, and the manufacturer has contraindicated its use in this population. An herbal tea containing chamomile, vervain, licorice, fennel, and balm-mint was also effective in a small RCT, but the volume necessary for treatment limits its usefulness (strength of recommendation: B, inconsistent or limited-quality patient-oriented evidence). The one proven treatment is time, as this behavior tends to dissipate by 6 months of age.