Effects Of Bethanechol Research Articles

The effect of bethanechol on tracheobronchomalacia in preterm infants with bronchopulmonary dysplasia: a retrospective cohort study.

Bethanechol has demonstrated improvement in trachealis tone in animal models, but no trials have studied efficacy in infants. This study aimed to examine if bethanechol improves a standardized pulmonary severity score (PSS) in infants with severe bronchopulmonary dysplasia with a diagnosis of tracheobronchomalacia (TBM). This retrospective cohort study evaluated cases treated with bethanechol matched with controls who did not receive bethanechol. TBM was diagnosed by dynamic computography. Daily PSS was recorded for each infant from 40 to 55 weeks post-menstrual age. Cases' mean PSS change was 21% lower than the controls' mean PSS change pre- and post-bethanechol (95% CI -40%, -2%) by paired t-test (p = 0.03). Matched differences (controls' PSS - cases' PSS) demonstrated greater mean PSS difference post-bethanechol compared to pre-bethanechol 0.17, (95% CI 0.05, 0.29) by paired t-test (p = 0.009). Infants with TBM treated with bethanechol compared to those not treated had a lower PSS reflecting improved respiratory status.

447 - The effect of bethanechol on tracheobronchomalacia in infants: A retrospective cohort study

447 - The effect of bethanechol on tracheobronchomalacia in infants: A retrospective cohort study

Bethanechol versus selegiline in amelioration of spinal cord injury in a rat model: A potential therapeutic option in spinal cord injury treatment

Purpose: To compare the effect of bethanechol versus selegiline in ameliorating spinal cord injury (SCI) in a rat model.Methods: Male adult Wistar rats (200 – 250 g) were equally divided into 3 groups: test (SCI rats treated with bethanechol), and control reference (SCI rats treated with selegiline) and control (SCI rats treated with vehicle). SCI was induced in the rats using the clipping method. Thereafter, motor function was assessed in the rats using a rotarod. Each rat was sacrificed by decapitation, and the cortex was excised for use in the study of the involvement of cholinergic and monoaminergic transmission in SCI rats using real-time quantitative polymerase chain reaction and western blot analysis.Results: Retention time was numerically greater in rats treated with acetyl choline agonist at all rotations (10, 15 and 25 rpm) when compared to MAO A inhibitor group, but the difference was not statistically significant (p > 0.05). Both bethanechol and selegiline improved motor function by increasing cholinergic and monoaminergic transmission. Both drugs (bethanechol and selegiline) were effective in ameliorating the motor function deficit caused by spinal cord injury. A significant upregulation in acetylcholine esterase (AChE) was observed in the cortex of the SCI rats, relative to non-SCI rats (p < 0.005). Results from cholinergic receptor binding studies revealed significantly decreased Bmax and kd values for muscarinic receptors in SCI rats, when compared to non-SCI rats. Moreover, the reduction in the intensity of cholinergic receptors was significantly higher in the cerebral cortex of SCI rats than in non-SCI rats.Conclusion: Bethanechol and selegiline are effective in ameliorating motor function deficit caused by spinal cord injury in rats. Both drugs also improve motor function in SCI rats. Therefore, the drugs have potentials for use in the therapeutical management of spinal cord injury.
 Keywords: Spinal cord injury, Bethanechol, Selegiline, Motor functions, Monoaminergic transmission, Cholinergic transmission

Evaluate the effect of bethanechol on blood glucose levels in euglycemic Wistar albino rats through oral glucose tolerance test

Objective: To evaluate the effect of bethanechol on blood glucose levels in euglycemic Wistar albino rats through oral glucose tolerance test (OGTT). Materials and Methods: Twelve Wistar albino rats weighing around 150-200 g of either sex were randomly selected from the central animal facility, and were divided into two groups. The control group received distilled water (25 mL/kg body wt.) per orally, test groups received bethanechol (3.6 mg/kg/day) per orally for 5 days. On the fifth day, following overnight fasting, 1 h after drug administration in all the groups of rats OGTT was performed, by administering oral glucose in dose of 0.6 gm/kg body weight. The capillary blood glucose (CBG) levels were measured at 0 min, 60 min, and 150 min, by rat tail snipping method using glucometer (ACCUCHEK). Results: The CBG levels of the bethanechol group was less when compared to the control group at all time intervals and the difference was statistically significant. Conclusion: Bethanechol showed the hypoglycemic activity when given for 5 days orally to euglycemic albino rats through OGTT.

In vitro effects of bethanechol on abomasal and duodenal smooth muscle preparations from dairy cows with left displacement of the abomasum and from healthy dairy cows

This study investigated the effects of bethanechol (BeCh) on abomasal and duodenal smooth muscle preparations from dairy cows with left displacement of the abomasum (LDA) and from healthy dairy cows, and determined the role of muscarinic acetylcholine receptor subtypes 2 and 3 (M(2) and M(3)) in mediating contraction. Concentration-response curves for BeCh, with or without prior incubation with an M(2) antagonist (AF-DX 116) or an M(3) antagonist (4-DAMP), were established and evaluated. BeCh induced a significant, concentration-dependant increase in the contractility variables for all locations in both groups of cows. The inhibiting effect of 4-DAMP was stronger than that of AF-DX 116, which suggested that contractions were mediated by M(3) and to a lesser extent by M(2). The basal tone of abomasal smooth muscle was reduced in cows with LDA, which indicated hypotonia. The use of BeCh as a prokinetic drug in cows with gastrointestinal motility disorder warrants further investigation.

The Effect of Bethanechol Chloride with an α-adrenergic Blocker in Patients with Impaired Detrusor Contractility

Purpose: Bethanechol enhances detrusor contraction and α1-blockers reduce bladder outlet resistance. We evaluated the effects of bethanechol with doxazosin in patients with impaired detrusor contractility. Materials and Methods: Fifty-six patients that had confirmed detrusor underactivity with at least 150ml of postvoid residual urine volume (PVR) based on a urodynamic study were enrolled. The initial dosage of bethanechol given was 75mg/day, and the dosage was gradually increased to 150mg/day if necessary. Doxazosin gastro-intestinal therapeutic system (GITS) (4mg) was also given. The effect of the treatment was evaluated by a urine flow test, the amount of PVR, and frequency of clean intermittent catheterization (CIC). Results: The mean follow-up period was 6 months (range, 1 to 9 months). After treatment, the mean PVR decreased from 251.8±149.6ml to 136.4± 153.2ml (p<0.001) and was less than 100ml in 22 (39%) of the 38 patients that showed a decrease. The maximum flow rate (Qmax) increased from 8.7±4.7ml/s to 11.1±5.6ml/s (p=0.024) and was more than 5ml/s in 13 patients (23%). Five of the 18 patients that previously required CIC could discontinue this treatment and another nine patients showed a decrease in the frequency. The mean daily frequency of CIC was reduced from 3.2 to 1.5 (p=0.004). Ten of the 12 patients that were not able to void became capable of voluntary voiding. Five patients (9%) complained of adverse reactions and four of them were taken off the medication. Conclusions: The combination therapy of bethanechol with doxazosin improved emptying ability in patients with impaired detrusor contractility. (Korean J Urol 2007;48:1040-1043) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Muscarinic Regulation of Ether-a-go-go-Related Gene K+ Currents in Interstitial Cells of Cajal

The interstitial cells of Cajal (ICC) of the myenteric plexus generate a set of currents that evoke a pacemaker potential that sets the initial conditions for the contraction frequency and duration of the electrically coupled intestinal musculature. The synapse-like contacts between ICC and myenteric motor nerves highlight the potential role of the enteric nervous system in regulating the pacemaking currents in ICC. The objective of the present study was to investigate muscarinic regulation of the ether-a-go-go-related gene (ERG) K(+) current. Immunoreactivity of the M(3) receptor (M(3)R) but not the M(2) receptor was detected on murine jejunal ICC-Auerbach's plexus (ICC-AP). The muscarinic agonist bethanechol reduced hyperpolarization-evoked peak ERG currents at -100 mV by 23 +/- 1% and increased both fast and slow time constants of deactivation, resulting in increased steady-state currents between -55 and -35 mV. Bethanechol also increased depolarization-evoked steady-state currents by 59 +/- 10% at -40 mV, whereas currents were decreased at potentials positive to 0 mV. The half-maximal voltage of activation was shifted 11.9 mV leftward. Interestingly, the time constant of activation increased only at -40 mV. Atropine prevented and 2 muM E4031 [1-[2-(6-methyl-2-pyridyl)-ethyl-4-(methylsulfonylaminobenzoyl)piperidine] inhibited bethanechol-affected currents. The effect of bethanechol was mimicked by protein kinase C (PKC) activation and diminished by PKC inhibition. Our results indicate that the ERG K(+) channel in ICC is affected by stimulation of muscarinic receptors, probably the M(3)R, via a PKC-dependent mechanism. Modulation of the ERG K(+) current in ICC-AP will affect the kinetics of pacemaking in the intestinal musculature.

Regulation of Drug Absorption from Small Intestine by Enteric Nervous System I: a Poorly Absorbable Drug Via Passive Diffusion

To investigate the regulation of drug absorption from the small intestine by the enteric nervous system (ENS), the vascular-luminal perfusion study and the in-vitro transport study were performed by employing phenol red as a poorly absorbable model compound. The effect of ENS on the intestinal absorption of phenol red was examined by adding epinephrine, an adrenergic agonist, or bethanechol, a cholinergic agonist into the vascular perfusate in the vascular-luminal perfused rat small-intestine preparation. The viability of the perfused intestine was checked by the recovery of the vascular perfusate, net water flux and absorbability of antipyrine, a well absorbable drug, and it was confirmed that the function of the perfused small-intestine preparation was maintained for at least 1 hr. The effect of epinephrine or bethanechol on the function of the small intestine was recognized as the increase in net water absorption, or the promotion of the water secretion, respectively. These phenomena are ones that are typically observed when adrenergic or cholinergic neuron is stimulated. Then, we investigated the small-intestinal absorption of phenol red in the vascular-luminal perfused preparation. Absorption clearance (CL(abs)) of phenol red was gradually increasing during the perfusion for 1 hr, but the 20-min vascular perfusion with the perfusate containing epinephrine made CL(abs) of phenol red constant and significantly lower than those for control study. Furthermore, after the perfusate was changed with the one without any agonist, again, CL(abs) of phenol red started to increase. These results clearly indicate that the stimulation of adrenergic neuron by epinephrine leads to the decrease in the small-intestinal absorption of phenol red. On the other hand, the vascular perfusion of bethanechol resulted in the increase in CL(abs) of phenol red comparing to the control study. Removing bethanechol from the vascular perfusate decreased CL(abs) of phenol red, again. The in-vitro transport study using the isolated jejunum sheet also showed that epinephrine in the serosal solution significantly decreased the transport of phenol red, which can be ascribed to the paracellular pathway tightened by the action of epinephrine because of the increase in transmucosal electrical resistance (TER). On the other hand, although the effect of bethanechol on both the transport of phenol red and TER was not statistically significant, the transport of phenol red tended to increase and the values of TER are smaller than those of control study.

Effects of bethanechol on canine urinary bladder smooth muscle function

We studied whether the effects of bethanechol are mediated via a muscarinic receptor, the role of extracellular calcium on bladder contraction, and down-regulation of bladder contraction by bethanechol after activation with potassium chloride (KCl) and acetylcholine (Ach). Smooth muscle strips of normal urinary bladder were studied with standard methods to measure isometric force. Bethanechol caused a dose-dependent increase in bladder contraction. The potency of bethanechol is higher than Ach, as shown by higher peak active isometric stress (Pmax) and lower half-maximal contraction (ED50) (P<0.01). The contractile responses to bethanechol were diminished in the presence of atropine, nifedipine and in calcium-free medium as shown by Pmaxdecreased by 58%, 87% and 65% andED50 increased by 314-, 24- and 16-fold, respectively. When bladder strips were stimulated with KCl and Ach, pre-treatment with bethanechol reduced the responses to KCl by 116–242% (P<0.05), while the contractile responses to Ach were unaltered. Thus, bethanechol induces bladder contraction via muscarinic receptor activation while both intracellular and extracellular calcium play a crucial role on bladder smooth muscle contraction. The mechanisms of down-regulation by bethanechol may be related to interference with calcium influx into the smooth muscle cells, rather than the desensitisation of muscarinic receptors or post-receptor steps of signal transduction following bethanechol binding to the receptor.

URETHRA IS MORE SENSITIVE TO ISCHEMIA THAN BLADDER: EVIDENCE FROM AN IN VITRO RAT STUDY

URETHRA IS MORE SENSITIVE TO ISCHEMIA THAN BLADDER: EVIDENCE FROM AN IN VITRO RAT STUDY

Lack of Beneficial Effects of Bethanechol, Imipramine or Furosemide on Seminal Plasma of Three Stallions with Urospermia

Lack of Beneficial Effects of Bethanechol, Imipramine or Furosemide on Seminal Plasma of Three Stallions with Urospermia

Lack of Beneficial Effects of Bethanechol, Imipramine or Furosemide on Seminal Plasma of Three Stallions with Urospermia

Lack of Beneficial Effects of Bethanechol, Imipramine or Furosemide on Seminal Plasma of Three Stallions with Urospermia

Effect of bethanechol, neostigmine, metoclopramide, and propranolol on myoelectric activity of the ileocecocolic area in cows

SUMMARY The effect of bethanechol, neostigmine, metoclopramide, and propranolol on myoelectric activity of the ileum, cecum, and proximal loop of the ascending colon was determined in 6 healthy Jersey cows implanted with 8 pairs of bipolar electrodes. Assigned at random, each cow received each of 5 treatments in 3-day intervals. The treatments included bethanechol (0.07 mg/kg of body weight, sc), neostigmine (0.02 mg/kg, sc), metoclopramide (0.15 mg/kg, im), dl-propranolol (0.2 mg/kg, im), and 0.9% sodium chloride (NaCl) solution (20 ml, sc). All drugs were administered during early phase I of the migrating myoelectric complex in the ileum. Myoelectric activity was recorded for 4 hours after treatment, and data were analyzed for each hour separately. Bethanechol and neostigmine significantly (P &lt; 0.05) increased the number of cecocolic spikes per minute per electrode, duration of cecocolic spike activity (%), and number of cecocolic propagated spike sequences per 10 minutes, relative to NaCl, during 1 or more hours of the recording period. The effect of bethanechol was more pronounced on duration of spike activity and number of propagated spike sequences, whereas neostigmine mainly increased the number of (uncoordinated) spikes. Metoclopramide and propranolol had no significant effect on cecocolic myoelectric activity, relative to NaCl. It was concluded that bethanechol and, less likely, neostigmine at the dosage used in this study may be suitable for medical treatment of cecal dilatation in cattle in which hypomotility of the cecum and proximal loop of the ascending colon has to be reversed. The potential advantage of bethanechol vs neostigmine for medical treatment of cecal dilatation is worth further evaluation.

A clinical trial of bethanechol in patients with xerostomia after radiation therapy: A pilot study

The effects of bethanechol in the treatment of dry mouth were assessed in patients with xerostomia after radiation therapy to the head and neck. Bethanechol possesses muscarinic and nicotinic-cholinergic activity that likely accounts for its mode of action. Bethanechol (25 mg, three times daily) was not associated with significant side effects. Statistically significant increases in whole resting saliva ( p = 0.003) and whole stimulated saliva ( p = 0.001) were seen. In patients with pretreatment stimulated saliva volumes greater than resting saliva volumes, a positive response to subsequent use of the sialagogue was seen.

Bethanechol-induced responses in mudpuppy parasympathetic neurons

The effect of bethanechol on membrane potential and excitability was determined in mudpuppy parasympathetic postganglionic neurons. Bethanechol induced a large amplitude hyperpolarization, which was followed by a smaller amplitude depolarization, in 115 out of 135 cells tested. In approximately 20% of these cells, a brief depolarization preceded the hyperpolarization. During the bethanechol-induced hyperpolarization, the membrane input resistance decreased markedly, whereas the input resistance was increased during the subsequent depolarization. The hyperpolarization and depolarization were blocked by atropine and were unaffected by d-tubocurarine, thus, both appeared to be mediated by muscarinic receptors. The bethanechol-induced hyperpolarization was inhibited by the M 2 muscarinic receptor antagonist AF-DX 116, whereas the bethanechol-induced depolarization was unaffected. Both a nonselective increase in membrane conductance and a decrease in membrane potassium conductance appeared to be involved in the generation of the bethanechol-induced depolarization. Evidence for the first mechanism was obtained in barium-treated cells in which bethanechol initiated a rapid onset depolarization, which was reversed at membrane potentials near 0 mV. Evidence for the second mechanism was obtained when the hyperpolarization was inhibited by AF-DX 116. In AF-DX 116-treated cells, the membrane input resistance was increased during most of the bethanechol-induced depolarization. Mudpuppy neurons initiate repetitive action potential activity in response to long depolarizing current pulses. Following application of bethanechol, with the hyperpolarization negated electrotonically, the number of action potentials produced by a depolarizing current pulse was greater than that produced prior to application of bethanechol. It is suggested that activation of muscarinic receptors on mudpuppy cardiac neurons influences multiple conductance systems and determines the excitability of these neurons.

Mucin and protein release in the rabbit jejunum: Effects of bethanechol and vagal nerve stimulation

The role of the vagus nerve and cholinergic mechanisms in the control of rabbit jejunal mucin and protein release was investigated in vivo. In anesthetized animals, a 10-cm segment of the jejunum was cannulated and perfused with saline. Perfusate was collected and analyzed for mucin (by immunoassay) and protein. Bilateral cervical vagotomy had no effect on basal mucin or protein output, suggesting that the vagus nerve does not exert a tonic control on jejunal macromolecule secretion. Electrical stimulation of the vagi did not alter mucin release, even in the presence of muscarinic cholinergic (scopolamine) or adrenergic (propranolol and phentolamine) blockade. In contrast, protein output increased significantly after vagal stimulation, an effect inhibited by scopolamine. In both vagotomized and vagally intact rabbits, the cholinergic agonist bethanechol (200 μg/kg intraperitoneally) induced a scopolamine-sensitive increase in both mucin and protein output. Predominantly serum proteins were released into intestinal perfusates after vagal or cholinergic stimulation. It is concluded that the extrinsic vagus nerve does not regulate rabbit jejunal mucin secretion in vivo and that cholinergic control of intestinal goblet cells is implemented entirely by the intrinsic enteric nervous system. In addition, cholinergic or vagal stimulation increases intestinal vascular and epithelial permeability, resulting in the passage of serum proteins into the lumen, possibly by opening tight junctions and paracellular pathways.

Bethanechol inhibition of chicken intestinal brush border Na/H exchange: role of protein kinase C and other calcium-dependent processes.

Bethanechol, a muscarinic agonist, inhibits the initial rate of amiloride-sensitive Na uptake by intact mucosa of avian small intestine as well as by isolated chicken villus enterocytes, an effect that is maximal at 90 seconds and reverses by 6 minutes. Bethanechol similarly decreases intracellular pH in isolated cells suspended in bicarbonate-free buffer in a time course similar to inhibition of enterocyte Na uptake, suggesting inhibition of Na/H exchange. In brush border membrane vesicles rapidly prepared from cells stimulated with bethanechol, proton-dependent 22Na uptake is transiently inhibited in a time course similar to inhibition of cell Na uptake. Bethanechol also stimulates transient translocation of protein kinase C from the cytosol to the particulate fraction, a portion of this activity translocating to the brush border membrane. To determine the calcium dependence of bethanechol's action, enterocytes were loaded with varying concentrations of the calcium buffering agent quin-2. Inhibition of cell Na uptake by the calcium ionophore ionomycin could be completely reversed by quin-2 buffering in a concentration-dependent manner. In contrast, quin-2 buffering had little or no effect on the inhibition of Na uptake caused by the protein kinase C activators phorbol esters and oleoylacetylglycerol. Bethanechol's inhibitory effects were partially, but not completely reversed by quin-2 buffering. These data suggest that the effects of bethanechol on chicken villus enterocyte brush border Na/H exchange are mediated by calcium-dependent process(es) as well as by protein kinase C.

Effect of bethanechol and vasoactive intestinal peptide (VIP) on the early production of inositol 1,4,5-triphosphate in intact colonic smooth muscle

Effect of bethanechol and vasoactive intestinal peptide (VIP) on the early production of inositol 1,4,5-triphosphate in intact colonic smooth muscle

Pharyngeal/upper esophageal sphincter pressure dynamics in humans

Extensive physiological studies of swallowing have been carried out in laboratory animals; however, similar studies in humans have been limited by available technology. In this study we describe the use of a solid-state circumferential sphincter transducer to define manometric characteristics of the human pharynx and upper esophageal sphincter (UES). Effects of pharmacologic agents and thermal stimulation are also described. We studied nine normal volunteers on three separate days. All studies were done in the upright position and consisted of a station pull-through of the UES and six wet swallows with the sphincter transducer in the most proximal segment of the UES and a posteriorly oriented single transducer 5 cm proximal in the pharynx. Baseline studies preceded all drug studies. Effects of bethanechol were studied on day 1, cold stimulation and benzonatate on day 2, edrophonium and atropine on day 3. The UES resting pressure showed large intrasubject day-to-day variations; however, mean values did not differ. There were no effects on UES relaxation or swallow coordination with any of the pharmacologic agents, although benzonatate produced multiple pharyngeal contractions.

Interaction of noradrenergic and cholinergic systems in regulation of ocular dominance plasticity

We studied interactions among the noradrenergic (NA) and the muscarinic cholinergic (ACh) systems in the regulation of ocular dominance plasticity in kitten visual cortex. The cortex was bilaterally infused with 6-hydroxydopamine (6-OHDA) for a week. Upon termination of the 6-OHDA infusion, one hemisphere was infused with a muscarinic ACh agonist, bethanechol, through the same, chronically implanted cannula for the second week together with monocular lid suture. The other hemisphere received an infusion of the vehicle solution alone. (1) Only in the hemisphere infused with bethanechol at relatively high concentrations did we obtain a clear shift in ocular dominance. We also found that the effect of bethanechol was concentration-dependent. (2) By comparing necessary concentrations of bethanechol and NA for the respective maximal effects, we noted that the former was at least 100-fold less effective than the latter in restoring the plasticity. (3) The cortical infusion of bethanechol did not restore the plasticity to the propranolol-pretreated cortex; the ocular dominance distribution remained virtually unchanged. This result was interpreted as suggesting that functioning β-adrenoreceptors are needed for the cortical effect of activating the muscarinic ACh receptors to become detectable. (4) The expected shift in ocular dominance following monocular deprivation was partially suppressed, when highly concentrated scopolamine, a muscarinic ACh antagonist, was used, indicating that the involvement of the ACh system in this matter was indirect. The concentration of scopolamine needed for the half-maximum effect was 172-fold higher than that of propranolol. We thus conclude that the involvement of the muscarinic ACh system in ocular dominance plasticity is secondary to that of the NA-β-adrenoreceptor system.