Bentyl
The mechanism of action of dicyclomine hydrochloride on rabbit detrusor muscle and vas deferens.

Johns A, Tasker JJ, Johnson CE, Theman MA, Paton DM.

Dicyclomine inhibited responses of rabbit detrusor muscle to transmural stimulation more than atropine or lidocaine, and also inhibited responses to acetylcholine and to KCl. Responses of rabbit vas deferens to noradrenaline and transmural stimulation were inhibited by dicyclomine. Dicyclomine was as potent a local anesthetic as lidocaine, as determined by the guinea-pig wheal test. 45Ca++ exchange in the rabbit detrusor, measured by the lanthanum methods, was not altered by atropine, lidocaine or dicyclomine. It is concluded that dicyclomine not only acts as an anticholinergic agent but also impairs excitation-contraction coupling and release of transmitter from autonomic nerves.

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Bentyl
The effect of M1 muscarinic blockade on behavior and physiological responses following traumatic brain injury in the rat.

Robinson SE, Foxx SD, Posner MG, Martin RM, Davis TR, Guo HZ, Enters EK.

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.

Dicyclomine (1 mg/kg or 10 mg/kg), scopolamine (1 mg/kg), or saline was administered intraperitoneally to rats 15 min prior to moderate fluid percussion brain injury. A variety of reflexes and responses were measured up to 60 min following injury, and body weight and several neurological measures were taken daily up to 10 days following injury. All 3 antimuscarinic treatments reduced the duration of transient behavioral suppression as assessed by these measures. It appears that blockade of the M1 muscarinic receptor can attenuate transient behavioral suppression associated with concussive brain injury. Thus, stimulation of M1 muscarinic receptors may mediate components of reversible traumatic unconsciousness following cerebral concussion. No differences were observed between saline and antimuscarinic treatments in the incidence or duration of apnea following injury. Scopolamine pretreatment significantly elevated heart rate prior to injury, but had no significant effect on the responses of heart rate and blood pressure to experimental concussion. Both doses of dicyclomine significantly reduced resting heart rate, but unlike scopolamine, significantly enhanced the cardiovascular response to fluid percussion injury. Antimuscarinic treatment significantly reduced body weight loss and certain motor deficits, including beam balance and beam walk performance, following concussive head injury. Scopolamine and both doses of dicyclomine appeared to be equally effective in reducing long-term deficits. Data from these experiments indicate that at least some of the long-term behavioral deficits following moderate levels of brain injury may involve the binding of acetylcholine to M1 muscarinic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

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Bentyl
Mini-pig urinary bladder function: comparisons of in vitro anticholinergic responses and in vivo cystometry with drugs indicated for urinary incontinence.

Peterson JS, Patton AJ, Noronha-Blob L.

Nova Pharmaceutical Corporation, Baltimore, Maryland 21224-2788.

1. Studies of carbachol-induced contractions on mini-pig bladder tissue strips in vitro demonstrated that antagonist drugs produced a rank order of potency similar to that observed in guinea-pig tissues: propantheline approximately atropine greater than oxybutynin greater than dicyclomine greater than HHSiD greater than imipramine greater than terodiline approximately AF-DX 116. The drugs appeared to show competitive antagonism and the tissues exhibited resistance to complete cholinergic blockade. 2. Cytometry performed in vivo on awake mini-pigs also showed that i.v. cholinergic antagonists produced a dose-dependent depression of peak intravesical bladder pressure (PvesP) during slow filling of the bladder using urethral catheters, with a rank order of potency: atropine greater than oxybutynin approximately propantheline greater than HHSiD approximately dicyclomine greater than terodiline. Other parameters of the cystometrogram were unaffected by the antagonists, except for residual volume, which generally increased after drug treatment. 3. Hexahydrosiladifenidol (HHSiD), an ileal-selective competitive muscarinic antagonist, was about as effective an antagonist as the clinically useful drugs oxybutynin or dicyclomine, both in vitro and in vivo, suggesting that HHSiD may have useful therapeutic effects for the treatment of urinary incontinence. 4. Correlation of the rank order of potency for muscarinic antagonism between mini-pigs and guinea-pigs was very high in vitro (r = 0.97, P less than 0.05), as was the correlation among the drugs for their ability to depress PvesP of the cystometrogram in vivo (r = 0.89, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

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Bentyl
Binding and functional profiles of the selective M1 muscarinic receptor antagonists trihexyphenidyl and dicyclomine.

Giachetti A, Giraldo E, Ladinsky H, Montagna E.

The selectivity profiles of the muscarinic receptor antagonists dicyclomine and trihexyphenidyl have been examined in binding and functional studies and compared with those of pirenzepine and atropine. Dicyclomine, trihexyphenidyl and pirenzepine demonstrated the highest affinity for the M1 muscarinic receptor subtype as revealed in competition experiments against [3H]-pirenzepine labelling of cortical membranes. Their affinity values lay in a narrow range (3.7-14 nM) approaching that of atropine (1.6 nM). Competition experiments against [3H]-N-methylscopolamine in cardiac and glandular (salivary) membranes revealed differences between the drugs examined. Dicyclomine, trihexyphenidyl and pirenzepine displayed low affinity for the cardiac and intermediate affinity for the glandular receptors. Thus, the drugs appeared to discriminate between the M1 (cortical) and the peripheral muscarinic subtypes (cardiac and glandular). However, atropine displayed similar affinities for either subtype with IC50s varying only slightly (1.6-4.6 nM). The rank order of selectivity was: pirenzepine greater than dicyclomine greater than trihexyphenidyl greater than atropine. Mirroring the binding data, pirenzepine, dicyclomine and trihexyphenidyl showed a tenfold greater ability at inhibiting M1-receptor mediated ganglionic responses (McN A-343 pressor effect in pithed rats and nictitating membrane contraction in cats) than at inhibiting peripheral muscarinic responses in the heart and cardiovascular smooth muscle (vagal bradycardia in rats and cats and vagally-induced vasodilatation in cats). The muscarinic antagonists so far examined can be categorized into two groups. Trihexyphenidyl, dicyclomine and pirenzepine, included in one group, are characterized by a higher affinity for the neuronal (M1) muscarinic receptor, hence they antagonize functional responses mediated by the M1 subtype. Atropine, a member of the other group, shows essentially no selectivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2432979&dopt=Abstract dicyclomine Bentyl