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PubMed1988

Positive bethanechol supersensitivity test in neurologically normal patients.

A positive bethanechol supersensitivity test (BST) usually indicates neuropathic detrusor areflexia and warrants neurologic correlation. Seven females, average age thirty-three years, with straining to void and high residual urines, had detrusor areflexia, with a borderline or positive BST, ranging from 19 cm water to 55 cm H2O change in intravesical pressure after 5 mg of subcutaneous bethanechol. However, all patients had a normal neurologic workup, even though 2 patients had insignificant spina bifida occulta. Two of the patients also had prior pelvic surgery, 1 of whom was azotemic, and 4 of the patients had psychosocial problems; factors reported to be associated with a false positive BST. The positive BST is not diagnostic of neurogenic detrusor areflexia because of the many variables that can influence the test. Therefore, the bethanechol supersensitivity test should be interrupted in light of the complete neurourologic evaluation.

Adult↗
PubMed1983

Intrahippocampal bethanechol in rats: behavioural, electroencephalographic and neuropathological correlates.

Unilateral microinjections of bethanechol chloride into the CA3 subfield of the dorsal hippocampus in unrestrained rats produced a seizure-related type behavioural and disseminated brain damage syndrome. Injection of bethanechol in the dose of 50 micrograms resulted in locomotor activation, mouth movements, teeth chattering, chewing, wet dog shakes and mild limbic seizures. Shortly after intrahippocampal injection the electroencephalogram (EEG) showed an increase in the frequency of the theta rhythm in both hippocampi. Then EEG showed spiking activity of high frequency in the injected hippocampus, with rapid propagation to the lateral septum, amygdala, neocortex and contralateral hippocampus. The periods of spiking activity of high frequency were followed by depression in the background EEG rhythm with some interspersed spike and wave complexes of very low frequency. Histological examination of frontal forebrain sections revealed disseminated, apparently seizure-mediated pattern of brain damage. The patterning of distant damage after intrahippocampal injections of bethanechol involved the piriform cortex, entorhinal cortex, olfactory tubercle, anterior olfactory nucleus, subiculum, amygdaloid complex, temporoparietal cortex and hypothalamic nuclei. Neuropathological alterations were occasionally observed in the lateral septum and thalamus. These results seem to establish a causative relationship between excessive stimulation of cholinergic muscarinic receptors in the hippocampal formation and epileptic brain damage.

Acetylcholine↗
PubMed1983

Neurogenic detrusor areflexia: correlation of perineal electromyography and bethanechol chloride supersensitivity testing.

We investigated 63 patients with detrusor areflexia by cystometrography, perineal floor electromyography and bethanechol chloride supersensitivity testing. Of the patients 48 had unequivocal evidence of neuropathy, while 15 were neurologically normal and served as controls. The bethanechol chloride supersensitivity test was positive in 98 per cent of the patients and none of the controls, whereas neuropathic changes by electromyography were found in 67 per cent of the patients and 7 per cent of the controls. These findings suggest that the bethanechol chloride supersensitivity test is more sensitive and more specific than perineal floor electromyography in corroborating bladder neuropathy.

Adult↗
PubMed1987

Effects of long-term medical treatment with cimetidine and bethanechol in patients with esophagitis and Barrett's esophagus.

To evaluate long-term medical therapy in patients with Barrett's esophagus, six patients were studied before and after long-term therapy with cimetidine for a mean period of 11.7 months. Some patients also received bethanechol. All had severe symptoms of gastroesophageal reflux resistant to intensive antacid therapy, specialized columnar epithelium by biopsy, and endoscopic evidence of severe inflammation. Esophageal manometry documented a hypotensive lower esophageal sphincter in three patients and low peristaltic amplitude in the distal esophagus in four. Treatment was begun with cimetidine, 300 mg orally four times daily. If symptoms did not totally abate, bethanechol, 25 mg orally four times daily, was added. Cimetidine completely relieved or dramatically reduced symptoms in all patients. Adding bethanechol produced further symptomatic improvement in three of four patients. After initial dilatation in the two patients with strictures, there was no recurrence. Endoscopic evidence of inflammation resolved completely in four patients and was markedly improved in two. Treatment with both drugs was well tolerated by all patients. The abnormally placed squamo-columnar junction did not regress during follow-up.

Adult↗
PubMed1991

Cumulative dose-response curves for bethanechol-induced electrogenic secretion in rat jejunum in vitro: is tachyphylaxis a significant factor?

Electrogenic secretion was monitored as the short-circuit current (Isc) by an automatic voltage clamp across the isolated rat jejunum incubated in vitro. Responses to consecutive additions of bethanechol (1 mM) to the serosal surface showed tachyphylaxis. Addition of prostaglandin E2, however, after a single dose of 1 mM-bethanechol, induced an undiminished Isc response indicating that the tachyphylaxis was homologous. Dose-response curves for serosal applications of bethanechol obtained by serial-cumulative addition did not show tachyphylaxis when compared with those from a non-cumulative technique. The method of automatically recording the intestinal Isc with serial-cumulative addition of a serosal secretagogue gives dose-response curves free from tachyphylaxis.

Animals↗
PubMed1992

Effects of anoxia on the biphasic response of isolated strips of rabbit bladder to field stimulation, bethanechol, methoxamine and KCl.

The contractile response of the bladder can be divided into two phases: an initial rapid increase in tension and a prolonged period of sustained tension (plateau phase). The bladder empties primarily during the plateau phase of the contractile response. These two phases can be differentiated using both pharmacologic and metabolic agents, indicating that the two phases have independent energy requirements. The present study compares the phasic (peak) and tonic (plateau) components of the responses of isolated strips of bladder body and base to field stimulation, bethanechol, methoxamine and KCl administration. New Zealand White rabbits were anesthetized with pentobarbital, and the bladder was removed. The bladder was divided between body and base at the level of the ureteral orifices. Three strips of bladder body and three strips of bladder base were mounted in separate baths containing Tyrode's solution at 37 degrees C and equilibrated with 95% O2, 5% CO2. Anoxia was produced by changing the gas mixture to 95% nitrogen, 5% CO2. The effects of anoxia on the responses to field stimulation, bethanechol, methoxamine and KCl were determined at different times after the initiation of anoxia. The results of these studies can be summarized as follows: (1) Anoxia induced time-dependent plateau phases of the response to field stimulation (2 and 32 Hz). (2) The rate of inhibition of the plateau phase was significantly and substantially greater than that of the peak phase in both the bladder body and base. (3) Similarly, anoxia inhibited the plateau phase of the bladder body's response to bethanechol to a significantly and substantially greater degree than anoxia inhibited the peak contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Treatment of nortriptyline's side effects in elderly patients: a double-blind study of bethanechol.

A double-blind, placebo-controlled study of bethanechol was conducted in 26 elderly depressed patients being treated with nortriptyline. Patients receiving bethanechol had reduced subjective complaints of anticholinergic side effects and showed a trend toward improvement on an objective measure of salivary flow. The potential use of bethanechol in older patients to reduce morbidity and improve compliance with medication regimens is discussed.

Aged↗
PubMed1981

Evaluation of elevation of the head of the bed, bethanechol, and antacid form tablets on gastroesophageal reflux.

To ascertain how elevation of the head of the bed, bethanechol, and antacid foam tablets affect gastroesophageal reflux, we used prolonged intraesophageal pH monitoring in 55 symptomatic patients. Acid exposure was separated into reflux frequency and esophageal acid clearance time and recorded during the day in the upright posture and recumbent at night. Values before and during each therapy were compared to physiologic reflux in 15 asymptomatic controls. Ten patients slept with the head of the bed elevated and had a 67% improvement in the acid clearance time (P less than 0.025); however, the frequency of reflux episodes remained unchanged. Twelve patients given 25 mg of bethanechol 4 times a day had a 50% decrease in recumbent acid exposure only (P less than 0.05), due to a trend towards decreased reflux episodes and acid clearance in time. Bethanechol combined with head of bed elevation in 19 other patients decreased both reflux frequency (30%) and acid clearance time (53%, all P less than 0.05). Antacid foam tablets failed to significantly diminish acid exposure. Nocturnal reflux responded the best to those therapies tested.

Antacids↗
PubMed2004

Expressions of CCAAT-enhancer-binding proteins and c-Myc in the parotid gland of the rat: in vivo effects of isoprenaline, bethanechol, vasoactive intestinal peptide and food intake.

Parotid glands of adult female rats were exposed to agonists mimicking sympathetic (isoprenaline, 1mg/kg, I.P.) or parasympathetic activity (bethanechol, 10 microg/kg/min i.v. for 30 min, and vasoactive intestinal peptide, VIP, 0.2 microg/kg/min, i.v. for 30 min) or they were reflexly activated by a meal demanding chewing. The stimulated glands were removed at varying times (15(30)-360 min) following the onset of the agonist administration or 75-300 min after the start of a 1h long feeding period, and a number of transcription factors was studied using Western blot. The protein bands were semi-quantitatively measured by densitometry. In response to isoprenaline, C/EBPalpha of 42, 38 and 30 kDa increased by 45-50% above control value, C/EBPbeta LAP (38/35 kDa) by 80% and C/EBPdelta (35 kDa) by 230%, while C/EBPbeta LIP (20 kDa) decreased by 45%. In response to VIP, C/EBPalpha of 42 kDa increased by 75% and C/EBPalpha of 30 kDa by 10%, C/EBPbeta LAP by 65% and C/EBPdelta by 410%, while C/EBPalpha of 38 kDa as well as C/EBPbeta LIP were not changed. In response to bethanechol, C/EBPalpha of 42 kDa increased by 105%, C/EBPbeta LAP by 40% and C/EBPdelta by 170%, while C/EBPalpha of 30 kDa decreased by 30% and C/EBPalpha of 38 kDa and C/EBPbeta LIP remained unchanged. c-Myc increased in response to isoprenaline and VIP by 40-55%, but not to bethanechol. In rats offered a pelleted diet, the parotid glands displayed increases in C/EBPalpha of 42 kDa by 105%, of 30 kDa by 40% and of 38 kDa, by 10%, in C/EBPbeta LAP by 65% and in C/EBPdelta by 215%, whereas C/EBPbeta LIP decreased by 25%. Thus, in parotid glands transcription factors of importance for growth and metabolism were shown to be influenced by autonomimetics as well as by nervous activity.

Animals↗
PubMed2004

The efficacy of pilocarpine and bethanechol upon saliva production in cancer patients with hyposalivation following radiation therapy.

PURPOSE: Pilocarpine and bethanechol have been reported as potentially effective sialogogues for xerostomic patients. The purpose of the present study was to compare the efficacy of bethanechol to that of pilocarpine in patients with dry mouth following cancer therapy. STUDY DESIGN: Patients with documented hyposalivation were provided pilocarpine or bethanechol for 2-3 weeks in an open-label randomized crossover study. Baseline and weekly whole resting saliva (WRS) and whole stimulated saliva (WSS) were obtained for 5 minutes. Subjective response and side effects were recorded. RESULTS: Forty-two xerostomic patients who had received radiation therapy to the head and neck participated. The increase in the WRS and WSS with each medication independently was limited. Statistically significant increase in WRS was seen for both medications when all patients using either agent were analyzed, but no statistically significant increase in WSS was found.Twenty-seven patients completed the crossover protocol. No significant difference in the effect was noted between each of the 2 drugs whether they were prescribed as the first or second drug in the crossover. Statistically significant improvement in subjective report of saliva production/mouth wetness was seen for patients on either medication. This study suggests that subjective improvement in symptoms of dry mouth may be related to resting saliva production, and not to stimulated saliva production. No statistically significant differences in adverse side effects were reported between the medications prescribed. The most common side effects were minor and included frequent urination, dizziness, and increased sweating. CONCLUSIONS: The findings indicate that head and neck radiation-treated patients with established hyposalivation will respond minimally to systemic sialagogues and while they may experience an increase in resting saliva little change in stimulated saliva may occur. It is not known whether relatively small increases in saliva are beneficial in maintaining oral health; however, subjective improvement suggests improved quality of life. While it is not known if prolonged use of a sialagogue will have increased effects, the limited increase in saliva seen following the second drug of the crossover suggests that prolonged use of a sialagogue may further increase saliva production.

Adult↗
PubMed1983

Results of treatment of gastroesophageal reflux with bethanechol.

Thirty-seven infants and children with gastroesophageal reflux were studied with prolonged esophageal pH monitoring before and during treatment with bethanechol. Total reflux scores improved by 69% (P = 6.47 X 10(-7) during bethanechol therapy. This improvement resulted primarily from decreases in the frequency and the duration of reflux episodes occurring more than two hours after feeding. Our findings indicate that infants and children with gastroesophageal reflux may safely be treated with bethanechol; thus the need for surgery is avoided.

Bethanechol Compounds↗
PubMed1978

Effects of bethanechol chloride on the external urethral sphincter in spinal cord injury patients.

The neuropharmacodynamics of bethanechol chloride on the external urethral sphincter in male spinal cord injury patients with chronic lesions have been investigated. There were 90 cystosphincterometric and sphincteroperineal electromyographic studies conducted on 45 subjects in 4 different positions, showing varying urodynamic patterns. A gross postural cystophincteric discordant reflex was noted in the majority of patients with recent complete upper motor neuron bladders (less than 2 years in duration). The external sphincter tends to be coordinated in late cases of quadriplegics and in all paraplegics. With the administration of bethanechol chloride there was an increase in the striated sphincter pressure profile when the patient was in the sitting position, resulting in detrusor sphincter dyssnergia. This phenomenon seems to be dose-related. When the dose of bethanechol chloride is adjusted according to the types of vesicourethral dysfunctions or in combination with dantrolene sodium the most beneficial non-surgical rehabilitation of the urinary tract can be obtained in this particular group of patients.

Adolescent↗
PubMed1998

Stability of bethanechol chloride, pyrazinamide, quinidine sulfate, rifampin, and tetracycline hydrochloride in extemporaneously compounded oral liquids.

The stability of five drugs commonly prescribed for use in oral liquids but not commercially available as such was studied. Bethanechol chloride 5 mg/mL, pyrazinamide 10 mg/mL, quinidine sulfate 10 mg/mL, rifampin 25 mg/mL, and tetracycline hydrochloride 25 mg/mL were each prepared in a 1:1 mixture of Ora-Sweet and Ora-Plus (Paddock Laboratories), a 1:1 mixture of Ora-Sweet SF and Ora-Plus, and cherry syrup and placed in 120-mL amber clear polyethylene terephthalate bottles. Three bottles of each liquid were stored at 5 degrees C and three at 25 degrees C, all in the dark. Samples were taken initially and at various times up to 60 days for analysis by high-performance liquid chromatography and assessment of appearance and odor; pH was measured. A mean of at least 90% of the initial drug concentration was retained for 60 days in the liquids containing bethanechol chloride, pyrazinamide, or quinidine sulfate and for 28 days in the rifampin-containing liquids and the mixture of tetracycline hydrochloride and Ora-Sweet-Ora-Plus at both 5 and 25 degrees C. Tetracycline hydrochloride concentrations of 90% or more of the initial concentration were retained in the liquids prepared with Ora-Sweet SF-Ora-Plus for 10 days at 5 degrees C and 7 days at 25 degrees C and in those prepared with cherry syrup for 7 days at 5 degrees C and 2 days at 25 degrees C. No substantial changes in the appearance, odor, or pH of any liquid were observed. At 5 and 25 degrees C, bethanechol chloride 5 mg/mL, pyrazinamide 10 mg/mL, and quinidine sulfate 10 mg/mL were stable in three extemporaneously compounded oral liquids for 60 days and rifampin 25 mg/mL was stable for 28 days. The stability of tetracycline hydrochloride 25 mg/mL varied with the vehicle.

Administration, Oral↗
PubMed1978

Smooth muscle mechanical responses in vitro to bethanechol after progesterone in male rat.

Male Sprague-Dawley rats were pretreated subcutaneously with either progesterone (3 mg/kg per day) in a vehicle or a vehicle only for 3 days. Antral and gastroduodenal junctional tissues (GJT) were excised from both groups of animals and prepared for in vitro mechanical measurements. Responses from the circular muscle axis of these tissues were recorded with strain gauge transducers over a 30-min period. Chemical stimulation of the tissue was achieved with a muscarinic agonist, bethanechol chloride. Log-dose response curves suggested that untreated antral tissue generated stronger contractile activity than untreated GJT on an equal weight basis at bethanechol dose levels of 6.4 X 10(-6) M to 1 X 10(-4) M (P less than 0.005). Antral tissue and GJT contractile activity from the progesterone pretreated animals was significantly reduced (P less than 0.01) compared to the corresponding tissues from untreated animals at bethanechol dose levels of 6.4 X 10(-6) M and 1.28 X 10(-5) M. Progesterone pretreatment appeared to have little effect on the contractile frequency of either tissue. These results suggest possible progesteronic influences on contractile force in gastrointestinal smooth muscle.

Animals↗
PubMed1983

Effects of bethanechol, metoclopramide, and domperidone on antral contractions in cats and dogs.

The effects of bethanechol, metoclopramide, and domperidone were examined on antral contractions in anesthetized dogs and cats. Bethanechol and metoclopramide were found to increase contractility in both the dog and cat, while domperidone did not stimulate contractions in the cat but was effective in the dog. With domperidone, unlike bethanechol and metoclopramide, changes in mean blood pressure were not produced. Our results indicate that all three of the agents examined can stimulate contractions in the antrum, but the choice of animal model is critical for the proper evaluation of the compounds.

Animals↗
PubMed1980

'Non-active' pepsin secretion compared with stimulated secretion by bethanechol, histamine, pentagastrin, and 2-deoxy-D-glucose. The role of vagal innervation.

The present studies were performed on a double-pouch dog with one vagally innervated Amdrup pouch (AP) and one denervated Heidenhain pouch (HP), allowing comparison of pepsin secretion from innervated and denervated mucosa at the same time in the same animal. 'Non-active' secretion of pepsin was determined by instillation in the pouches of 0.1 M and 0.005 M HCl, 0.15 M NaCl, and 0.03 M phosphate buffer, and well-known stimulators of gastric secretion such as histamine, pentagastrin, bethanechol, and 2-deoxy-D-glucose (2-DG) were tested as pepsigogues. Cholinergic stimulation by 2-DG and bethanechol (Urecholine) was clearly the most potent stimulus of pepsin secretion. 2-DG elicited secretion only from innervated mucosa, whereas the responses to bethanechol were similar in the two pouches. Histamine and pentagastrin were weak stimulators, but both provoked active and sustained secretion of pepsin when given in small doses. Higher doses of histamine strongly inhibited pepsin output. The effects of histamine were independent of vagal innervation. By contrast, the active stimulation by pentagastrin only took place in innervated mucosa. The highest outputs were seen in the lowest doses, but also very high doses of pentagastrin elicited active pepsin secretion in the AP. Medium doses of pentagastrin brought the secretion down the the 'non-active' level. The chief cells in the denervated mucosa were quite insensible to pentagastrin, and the pepsin output in the HP equalled the non-active' response at all dose levels.

Animals↗
PubMed1982

Effect of dopamine on bethanechol-stimulated gastric mucosal blood flow and gastric acid secretion in dogs with gastric fistula.

The aim of the present study was to investigate the effect of Dopamine on bethanechol-stimulated gastric acid secretion and mucosal blood flow. dopamine was used alone and in conjunction with selective blockade of the alpha, beta, and dopaminergic receptors. An increasing and dose-dependent stimulation of gastric acid secretion was found for dopamine at 1, 5, and 10 micrograms/kg/min. A significant inhibition of gastric acid secretion was found with the highest dose of dopamine (40 micrograms/kg/min). the stimulatory effect seems to be mediated by more than one receptor, whereas the inhibition by high dopamine doses could be explained by a beta 1 stimulation. Dopamine (10 micrograms/kg/min) was found to increase the bethanechol-stimulated gastric mucosal blood flow. Phentolamine (alpha blackade) increased this dopamine-elevated blood flow further, with a significant increase in the ratio between blood flow and acid secretion, indicating a primary action of the alpha receptors on blood flow. Bethanechol stimulated the gastric acid secretion and blood flow in a parallel manner. It is concluded that alpha-receptor stimulation is the predominant directly acting factor in the regulation of gastric mucosal blood flow, whereas stimulation of beta, muscarinic, and 'gastrinergic' receptors mainly occurs indirectly via changes in parietal cell function. The main effect of dopamine seems to be on gastric motility, whereas the effect on gastric acid secretion is of minor importance.

Animals↗
PubMed1985

Effect of somatostatin on bethanechol-stimulated gastric pepsin secretion in gastric fistula dogs.

The effect of somatostatin on pepsin secretion was determined in six dogs with gastric fistulas during stimulation with bethanechol. Somatostatin inhibited dose-dependently the stimulated pepsin secretion, with a dose of 0.3 micrograms/kg/h being 35% inhibitory during stimulation with bethanechol, 80 micrograms/kg/h. Continuous infusion of somatostatin for 3 h did not cause any signs of tachyphylaxis. Withdrawal of somatostatin produced a return to the control level. The dose-response kinetics with five doses of bethanechol with and without somatostatin showed inhibition of a noncompetitive type. The effects of somatostatin were not altered by using adrenergic, dopaminergic, or serotonergic blocking drugs.

Adrenergic beta-Antagonists↗