Bentyl
Facilitatory and inhibitory muscarine receptors on the rat phrenic nerve: effects of pirenzepine and dicyclomine.

Wessler I, Diener A, Offermann M.

Pharmakologisches Institut, Universitat Mainz, Federal Republic of Germany.

Neuronal transmitter stores of the rat phrenic nerve were labelled by an incubation with [3H]choline. Release of [3H]acetylcholine was elicited either by a short (100 pulses, 5 Hz) or by a long (1500 pulses, 5 or 25 Hz) period of electrical nerve stimulation. Pirenzepine and dicyclomine enhanced transmitter release evoked by the short stimulation period. Both antagonists reduced transmitter release evoked by the long stimulation period. Pirenzepine reduced transmitter release at low concentrations (1 nmol/l) whereas a higher concentration was necessary for the enhancing effect; the opposite pattern was found for dicyclomine. A low concentration of oxotremorine (10 nmol/l) enhanced and a high concentration (1 mumol/l) reduced transmitter release evoked by the short stimulation period. Both effects could be prevented by a low concentration of pirenzepine (10 nmol/l). It is concluded that facilitatory and inhibitory muscarine receptors are present on the motor nerve. A short stimulation period activates predominantly the negative muscarinic feedback, whereas during a long period of continuous nerve stimulation the positive muscarinic feedback mechanism is additionally activated. Both the facilitatory and inhibitory receptors might be regarded as M1-receptors but differences in the pharmacological properties between both receptor populations appear possible.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2847058&dopt=Abstract dicyclomine Bentyl



Bentyl
Dicyclomine discriminates between M1- and M2-muscarinic receptors in the guinea-pig ileum.

Kilbinger H, Stein A.

Pharmakologisches Institut Universitat, Mainz, F.R.G.

1. The affinity of the antagonist dicyclomine for subtypes of muscarinic receptors has been assessed in the myenteric plexus-longitudinal muscle preparation of the guinea-pig. 2. Dicyclomine had a high affinity (pA2 9.13) for the neuronal M1-receptor whose activation by pilocarpine causes an increase in acetylcholine release. Dicyclomine had a low affinity for both the prejunctional M2-receptor (pA2 7.61) mediating inhibition of the electrically-evoked acetylcholine release and the postjunctional M2-receptor (pA2 7.21). 3. It is concluded that dicyclomine distinguishes between M1- and M2-muscarinic receptors in functional experiments.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3207984&dopt=Abstract dicyclomine Bentyl



Bentyl
Dicyclomine, an M1 muscarinic antagonist, reduces infarct volume in a rat subdural hematoma model.

Jiang ZW, Gong QZ, Di X, Zhu J, Lyeth BG.

Division of Neurosurgery, Medical College of Virginia Campus, Virginia Commonwealth University Richmond, USA.

The rat subdural hematoma (SDH) model produces a zone of ischemic brain damage within the hemisphere beneath the SDH. Previous studies have measured large increases in extracellular acetylcholine during cerebral ischemia in the rat. We examined infarct volume after selectively blocking muscarinic M1 receptors with dicyclomine during SDH. Rats were anesthetized with isoflurane (2%), intubated, and femoral artery and vein cannulated. Autologous blood (0.375 ml) was injected (0.05 ml/min) under the dura of the right parietal cortex. Dicyclomine (5 mg/kg, i.v.) was injected at 5 min after and again at 2 h after completion of the subdural blood infusion. Blood pressure and intracranial pressure (ICP) were continuously measured. At 4 h after SDH rats were euthanized, brains sectioned, and immunoreacted with glia fibrillary acidic protein. Cortical infarct volume was quantified in coronal brain sections at 0.7-mm intervals from +1.0 mm to -3.9 mm relative to bregma. Infarct volume in drug-treated rats (n = 10) 22.1 +/- 6.99 mm3 was significantly smaller (p < 0.02) than vehicle treated rats (n = 10) 56.7 +/- 9.59 mm3. ICP, blood pressure and cerebral perfusion pressure were not significantly different between groups. These data suggest that activation of M1 muscarinic receptors during an ischemic event may contribute to the development of subsequent pathology.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10661493&dopt=Abstract dicyclomine Bentyl



Bentyl
Dicyclomine, benzhexol and oxybutynine distinguish between subclasses of muscarinic binding sites.

Nilvebrant L, Sparf B.

The interactions of various unlabelled antimuscarinic drugs with the muscarinic receptors in the cerebral cortex, heart and urinary bladder were studied by a receptor binding technique, using (-)[3H]QNB as radioligand. In contrast to the other drugs examined, dicyclomine, benzhexol, oxybutynine and pirenzepine were bound with a significantly higher affinity in the cortex than in the heart and bladder. Furthermore, not only pirenzepine, but also dicyclomine and benzhexol were capable of distinguishing between two populations of muscarinic binding sites in the cortex. The low affinity sites for these drugs in the cortex were characterised by dissociation constants which were similar to those determined in the heart and the bladder, respectively. It was concluded that dicyclomine and benzhexol, like pirenzepine, are selective antagonists at the putative M1-receptor. Oxybutynine exhibited the same affinity profile but the tissue selectivity of this drug was less pronounced.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3754815&dopt=Abstract dicyclomine Bentyl