Bentyl
Congenital anomalies in relation to the use of doxylamine/dicyclomine and other antenatal factors: an ongoing prospective study.

Gibson GT, Colley DP, McMichael AJ, Hartshorne JM.

Recent publicity regarding possible teratogenic effects of the doxylamine/dicyclomine/pyridoxine combination (Debendox) has led to a degree of apprehension in women for whom the drug is prescribed, and in doctors who prescribe it. This study, based on an ongoing epidemiological surveillance programme, reports an analysis of the records of 1817 women for whom the drug was prescribed compared with 5771 non-users. The object of the study was to evaluate the outcome of pregnancy against exposure to the drug, taking into account the coexistent influences of other factors. Thorough statistical analysis disclosed no evidence of teratogenicity of the doxylamine/dicyclomine/pyridoxine overall, nor in relation to the skeletal or cardiovascular systems in particular. Two unexpected findings were an apparent moderate increase in genital tract abnormalities in users of this drug, and the possibility of a synergistic relationship between tobacco and this drug in early pregnancy, both aspects warranting further investigation.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7254087&dopt=Abstract dicyclomine Bentyl



Bentyl
Antagonism of calcium-induced contraction in potassium-depolarized rabbit detrusor muscle strips by dicyclomine hydrochloride and rociverine.

Downie JW, McGuire RP.

The musculotropic action of dicyclomine hydrochloride in bladder muscle has been attributed to its local anesthetic activity. In this study rabbit detrusor strips were depleted of calcium by incubation in Ca2+-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA). Contractions elicited by replacement of Ca2+ during depolarization with 80 mM K+ were only slightly affected by atropine or scopolamine but were antagonized in a noncompetitive manner by dicyclomine and rociverine (pD2' = 4.89 and 4.61, respectively). These contractions were also blocked with greater potency by nifedipine (pD2' = 8.50) and with lesser potency by lidocaine (pD2' = 2.52). Procaine was ineffective up to 1 mM. Comparison of the antagonism produced by dicyclomine and rociverine with that produced by nifedipine or lidocaine did not help to define the mechanism of the musculotropic drugs. However, as rociverine is not a local anesthetic and procaine was not effective, it appears that the "local anesthetic" property is not sufficient to explain the action of these musculotropic drugs.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7296384&dopt=Abstract dicyclomine Bentyl



Bentyl
Antimuscarinic and noncompetitive antagonist properties of dicyclomine hydrochloride in isolated human and rabbit bladder muscle.

Downie JW, Twiddy DA, Awad SA.

In isolated strips of bladder neck (prostatic capsule) and detrusor of rabbit and man, dicyclomine had minimal effect on the resting tension. Competitive antimuscarinic activity against carbachol could be demonstrated at doses of dicyclomine less than or equal to 1 X 10(-6) M, whereas at higher doses a noncompetitive action against both carbachol and potassium was observed. The ratio of dissociation constants relating to the noncompetitive and competitive actions, respectively, was about 1200, approximately 100 times higher than that previously reported in ileum. Dicyclomine was only about 1/30 as potent as atropine in competitive antimuscarinic activity. Dicyclomine hydrochloride may be useful in the clinical management of "uninhibited bladder."

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=864602&dopt=Abstract dicyclomine Bentyl



Bentyl
Pharmacological characterization and distribution of muscarinic receptors in human placental syncytiotrophoblast brush-border and basal plasma membranes.

Pavia J, Munoz M, Jimenez E, Martos F, Gonzalez-Correa JA, De la Cruz JP, Garcia V, Sanchez de la Cuesta F.

Department of Pharmacology, Malaga School of Medicine, Malaga University, Spain. Pavia ccuma.sci.uma.es

Based on the existence of choline acetyltransferase and acetylcholine in human placenta, we have investigated the presence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta. Radioligand binding assay, using [3H]N-methyl-scopolamine as tracer, showed the existence of acetylcholine muscarinic receptors in brush-border (Kd 0.28 +/- 0.04 nM; Bmax 9.4 +/- 1.6 fmol/mg protein) and basal plasma membranes (Kd 0.24 +/- 0.05 nM; Bmax 34.3 +/- 6.3 fmol/mg protein). In order to perform a pharmacological characterization of these receptors, competition binding experiments were carried out using the muscarinic receptor antagonists pirenzepine, (11(2-diethyl-amino)methyl)-1-piperidinylacetyl-5-11-dihydro-6H-py rido(14) benzodiazepine (AF-DX 116), himbacine, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), dicyclomine and hexahydro-sila-difenidol (HHSD). The results obtained showed that the muscarinic receptors in brush-border and basal plasma membranes belong to different subtypes. In brush-border membranes, the receptor found match in terms of affinity for the antagonists with the muscarinic M1 receptor subtype (Ki pirenzepine, 13.6 +/- 8.2 nM; Ki AF-DX 116, 1680 +/- 271 nM; Ki himbacine, 212 +/- 6.5 nM; Ki 4-DAMP. 1.5 +/- 0.4 nM; Ki dicyclomine, 5.1 +/- 0.8 nM; Ki HHSD, 34.3 +/- 7.3 nM), whereas the receptor in basal plasma membrane seems to be of the muscarinic M2 receptor subtype (Ki pirenzepine, 202 +/- 48 nM; Ki AF-DX 116, 124 +/- 60 nM; Ki himbacine, 20.6 +/- 4.8 nM; Ki 4-DAMP, 4.5 +/- 1.2 nM; Ki dicyclomine, 54.6 +/- 22 nM; Ki HHSD, 89.2 +/- 15.8 nM). The results obtained show the existence of muscarinic acetylcholine receptors in brush-border and basal plasma membranes from human term placenta with a different distribution pattern in terms of number of receptors and distribution of different subtypes. The functional significance of these findings is as yet unknown, but these receptors probably mediate different functions as they belong to different subtypes and are coupled to different second messengers.

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Bentyl
Antiamnesic activity of metoclopramide, cisapride and SR-17 in the mouse passive avoidance test.

Galeotti N, Ghelardini C, Teodori E, Gualtieri F, Bartolini A.

Department of Preclinical and Clinical Pharmacology, University of Florence, Italy.

The effects of the administration of metoclopramide, cisapride and SR-17 on memory processes were evaluated in the mouse passive avoidance test. The administration of dicyclomine (0.1-3 mg kg-1 i.p.), immediately after termination of the training session, produced a dose-dependent amnesic effect. Metoclopramide (1-5 mg kg-1 i.p.), cisapride (0.5-2 mg kg-1 i.p.) and SR-17 (1-10 mg kg-1 i.p.), administered 20 min before the training session, prevented dicyclomine-induced amnesia. In the same experimental conditions piracetam (30 mg kg-1 i.p.), physostigmine (0.2 mg kg-1 i.p.) and CGP 35348 (100 mg kg-1 i.p.) prevented dicyclomine amnesia. At the highest effective doses, none of the drugs impaired motor coordination, as revealed by the rota-rod test, nor did they modify spontaneous motility, as revealed by the Animex test. These results suggest that metoclopramide, cisapride and SR-17 play an important role in the modulation of memory processes. On these bases, these compounds could be useful in the treatment of cognitive deficits.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9368916&dopt=Abstract dicyclomine Bentyl