Comparison of the effects of atropine and glycopyrrolate on various end-organs. (73/86)

Atropine and glycopyrrolate (glycopyrronium bromide), a quaternary ammonium drug, were evaluated in volunteers following intramuscular administration with respect to effects on various end-organs with cholinergic innervation. Glycopyrrolate appears to be five to six times more potent than atropine in its antisialogogue effect and also exhibits a selective, though prolonged, effect on salivary secretion and sweat gland activity. It has minimal cardiovascular, ocular and central nervous system effects.  (+info)

Survival under hypoxia. Age dependence and effect of cholinergic drugs. (74/86)

Survival under hypoxia (5% O2; 95% N2) was tested in mice 1 day to 50-weeks-old. Survival Rate (ratio of number of animals that survived 30 min under 5% O2 to total number of animals exposed) and the time from onset of exposure until the last gasp (Survival Time) were maximum in newborn animals and decreased as a function of age. Survival Rate and Survival Time were strongly influenced by drugs affecting cholinergic transmission. Atropine decreased the high survival under hypoxia of 1-week-old mice in a dose-related manner. Physostigmine increased survival under hypoxia in mice 3 to 50-weeks-old. This effect was not related to a peripheral action of the drug since it was not mimicked by neostigmine, a cholinesterase inhibitor without central actions. Moreover, peripheral cholinergic blockade with glycopyrrolate, a quaternary cholinergic blocker, did not prevent the protective effect of physostigmine. Since atropine impairs the ability of very young mice to survive hypoxia and physostigmine improves survival at later ages, it is concluded that a central cholinergic mechanism, possibly related to blood flow regulation, plays a significant role in the acute adaptation to hypoxia.  (+info)

Vagal modulation of epicardial coronary artery size in dogs. A two-dimensional intravascular ultrasound study. (75/86)

BACKGROUND: Because the role of tonic vagus nerve activity in regulating conduit coronary artery size remains undefined, we investigated the response of epicardial coronary artery size to changes in resting vagal tone resulting from vagotomy and muscarinic receptor blockade. METHODS AND RESULTS: Using intravascular ultrasound to measure left circumflex coronary artery cross-sectional area continuously, we examined the effects of vagotomy on left circumflex cross-sectional area in nine dogs. Lumen area decreased 20% from 8.70 +/- 2.81 to 6.92 +/- 1.97 mm2 after right vagotomy, 17% to 7.19 +/- 2.80 mm2 after left vagotomy (both P < .05 versus baseline), and 38% to 5.42 +/- 2.00 mm2 after bilateral vagotomy (P < .05 versus unilateral vagotomy). Vasoconstriction occurred despite increases in heart rate and an unchanged rate-pressure product. In six additional dogs, after acetylcholine (100 micrograms/kg i.v.), lumen area increased by 18%, although heart rate, blood pressure, and rate-pressure product were unchanged. Vasodilation was prevented by prior muscarinic blockade with glycopyrrolate. With glycopyrrolate administration and heart rate control by pacing, lumen area decreased by 26% (P = .011). When stellate stimulation was performed in a third group of eight dogs with heart rate, blood pressure, and rate-pressure product controlled by a combination of pacing and exsanguination, there was no change in coronary area, thus precluding reflex sympathetic activation as a contributor to the vasoconstriction produced by vagal withdrawal. CONCLUSIONS: Vagus nerve activity maintains tonic dilation of the left circumflex coronary artery by muscarinic receptor activation. Each vagus nerve contributes approximately equally to the tonically dilated state. Vagotomy-induced vasoconstriction occurs independently of local metabolic factors and coronary distending pressure and is a result of cholinergic withdrawal rather than reflex sympathetic activation.  (+info)

Atropine and glycopyrronium show similar binding patterns to M2 (cardiac) and M3 (submandibular gland) muscarinic receptor subtypes in the rat. (76/86)

Atropine and glycopyrronium are frequently used for premedication to reduce oral and respiratory secretions and prevent bradycardia. Glycopyrronium is said to have similar antisialagogue effects, but is less likely to cause significant tachycardia than atropine. Different antimuscarinic receptor selectivity patterns could explain the differences. The aim of this investigation was to determine the possible selectivity of glycopyrronium for M2 and M3 muscarinic receptor subtypes. Muscarinic receptor subtypes in Wistar rat ventricle and submandibular gland homogenates were characterized with [3H]-N-methylscopolamine ([3H]-NMS) by ligand binding studies. Inhibition of [3H]-NMS binding by non-labelled compounds showed the following order: in rat ventricle: glycopyrronium > atropine >> otenzepad > hexahydrosiladiphenidol (HHSiD) > pirenzepine; in rat submandibular gland: glycopyrronium > atropine >> HHSiD >> pirenzepine > otenzepad. These were similar to the expected order of frequency of M2 and M3 subtypes, respectively. Glycopyrronium showed similarly high affinities for both M2 (Ki = 1.889 (SEM 0.049) nmol litre-1) and M3 (Ki = 1.686 (0.184) nmol litre-1) subtypes. Glycopyrronium bound to a homogeneous population of binding sites in both tissues and showed no selectivity for M2 or M3 muscarinic receptor subtypes.  (+info)

Reduced beta-adrenergic receptor activation decreases G-protein expression and beta-adrenergic receptor kinase activity in porcine heart. (77/86)

To determine whether beta-adrenergic receptor agonist activation influences guanosine 5'-triphosphate-binding protein (G-protein) expression and beta-adrenergic receptor kinase activity in the heart, we examined the effects of chronic beta 1-adrenergic receptor antagonist treatment (bisoprolol, 0.2 mg/kg per d i.v., 35 d) on components of the myocardial beta-adrenergic receptor-G-protein-adenylyl cyclase pathway in porcine myocardium. Three novel alterations in cardiac adrenergic signaling associated with chronic reduction in beta-adrenergic receptor agonist activation were found. First, there was coordinate downregulation of Gi alpha 2 and Gs alpha mRNA and protein expression in the left ventricle; reduced G-protein content was also found in the right atrium. Second, in the left ventricle, there was a twofold increase in beta-adrenergic receptor-dependent stimulation of adenylyl cyclase and a persistent high affinity state of the beta-adrenergic receptor. Finally, there was a reduction in left ventricular beta-adrenergic receptor kinase activity, suggesting a previously unrecognized association between the degree of adrenergic activation and myocardial beta-adrenergic receptor kinase expression. The heart appears to adapt in response to chronic beta-adrenergic receptor antagonist administration in a manner that would be expected to offset reduced agonist stimulation. The mechanisms for achieving this extend beyond beta-adrenergic receptor upregulation and include alterations in G-protein expression, beta-adrenergic receptor-Gs interaction, and myocardial beta-adrenergic receptor kinase activity.  (+info)

The parasympatholytic effects of atropine sulfate and glycopyrrolate in rats and rabbits. (78/86)

Nine groups of rats (n = 5 per group) received an intramuscular (IM) injection of one of the following drugs or drug combinations: saline, atropine (0.05 mg/kg), glycopyrrolate (0.5 mg/kg), ketamine:xylazine (85:15 mg/kg), ketamine:detomidine (60:10 mg/kg), atropine:ketamine:xylazine (0.05: 85:15 mg/kg), glycopyrrolate: ketamine:xylazine (0.5:85:15 mg/kg), atropine:ketamine:detomidine (0.05: 60:10 mg/kg) or glycopyrrolate: ketamine:detomidine (0.5:60:10). Similarly six groups of rabbits (n = 5) received an IM injection of either saline, atropine (0.2 mg/kg), atropine (2 mg/kg), glycopyrrolate (0.1 mg/kg), ketamine:xylazine (35:10 mg/kg) or glycopyrrolate:ketamine:xylazine (0.1:35:10 mg/kg). In rats, atropine sulfate (0.05 mg/kg) and glycopyrrolate (0.5 mg/kg) produced an increase in heart rate for 30 and 240 min, respectively. In rabbits atropine sulfate at either 0.2 or 2.0 mg/kg did not induce a significant increase in heart rate, but glycopyrrolate (0.1 mg/kg) elevated the heart rate above saline treated animals for over 50 min. Both atropine and glycopyrrolate provided protection against a decrease in heart rate in rats anesthetized with ketamine: xylazine (85:15 mg/kg) or ketamine: detomidine (60:10 mg/kg); however, glycopyrrolate was significantly more effective in maintaining the heart rate within the normal range. Glycopprrolate also prevented a decrease in heart rate in rabbits anesthetized with ketamine:xylazine (35:5 mg/kg). Neither glycopyrrolate nor atropine influenced respiration rate, core body temperature or systolic blood pressure when used alone or when combined with the injectable anesthetic. Glycopyrrolate is an effective anticholinergic agent in rabbits and rodents and more useful as a preanesthetic agent than atropine sulfate in these animals.  (+info)

Comparison of nebulized glycopyrrolate and metaproterenol in chronic obstructive pulmonary disease. (79/86)

We assessed the bronchodilating effect of glycopyrrolate (GP) and compared it with that of metaproterenol (MP), alone and in combination (GP+MP), in patients with chronic obstructive pulmonary disease (COPD). In a double-blind study, 11 patients (aged (mean +/- SD) 69 +/- 6 yrs; forced expiratory volume in one second (FEV1) 1.2 +/- 0.4 L) with stable COPD inhaled nebulized GP 1.0 mg, MP 15 mg, or GP 1.0 mg+MP 15 mg. Spirometry was performed before inhalation and at hourly intervals for 8 h after inhalation. It was found that GP produced a bronchodilating effect that was about equal to that of MP but lasted longer (8 vs 5 h). The combination of GP and MP produced a bronchodilating effect that was greater than that of either drug alone and was evident mostly during the effect of MP. The mean peak percentage improvement in FEV1 over baseline was 35% for GP+MP and 25% for either drug alone. These data suggest that nebulized glycopyrrolate is an effective bronchodilator in some patients with chronic obstructive pulmonary disease. Concurrent administration of glycopyrrolate and metaproterenol produces additional bronchodilation that is primarily apparent during the bronchodilator effect of metaproterenol.  (+info)

Management of secretions in esophageal cancer patients with glycopyrrolate. (80/86)

BACKGROUND: There has been little emphasis in the past upon management of excessive secretions in patients with esophageal cancer. We used the drug glycopyrrolate for controlling secretions in patients with esophageal cancer. PATIENTS AND METHODS: Between January 1991 and September 1995, 45 patients with esophagus cancer were referred for evaluation. Seven of these patients were treated with glycopyrrolate for increased secretions. Secretions were measured in suction canisters which were used by patients. RESULTS: All the patients showed a decrease in secretions within 24 48 hours of administration. The incidence of side effects was minimal. CONCLUSIONS: Glycopyrrolate is quite effective in palliating esophageal cancer patients with excessive secretions.  (+info)