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At least 145 records · Page 8Linked to original sources
PubMed1998

Do parasympatholytic effects of long-acting beta 2-sympathomimetics contribute to their relaxant effects in airway smooth muscle cells?

To address the hypothesis of whether functional antagonistic effects of long-acting beta 2-sympathomimetics (formoterol and salmeterol) might be supported by direct antagonistic effects on muscarinic acetylcholine receptors (mAChR), we performed radioligand binding experiments with 3H-quinuclidinyl-benzilate in membranes of airway smooth muscle cells (calf tracheal myocytes). beta 2-Sympathomimetics (short- and long-acting) were compared to catechol-ethanolamines and catechol-ethylamines. Tracheal myocytes were characterized by a high density of mAChR 1017 +/- 17 fmol/mg, which exceeds that of beta 2-adrenoceptors 20-fold. The affinities of drugs were determined by competition binding. Dissociation constants ¿pKD-values) of formoterol (5.04 +/- 0.05) and salmeterol (5.24 +/- 0.04) matched that of ACh (5.37 +/- 0.03) and were significantly higher than that of the mAChR-agonist carbachol (4.65 +/- 0.03). pKD-values of mAChR-agonists were strictly dependent on GTP-concentration (> 50-fold difference between high- and low-affinity states), in contrast to those of formoterol, thereby characterizing formoterol as an mAChR-antagonist. A 10-fold lower affinity of the related compound fenoterol (3.94 +/- 0.02) hinted at the formyl-amino moiety of formoterol as a structural determinant of high-affinity whereas a 100-fold lower affinity of salbutamol as compared to salmeterol suggested the aliphatic side chain was a structural determinant of high affinity. The high affinity of dobutamine (4.96 +/- 0.02) and dopexamine (6.20 +/- 0.02) provided evidence that high affinity can be found not only for catechol-ethanolamines with long side chains but also for catechol-ethylamines. The question of whether high local concentrations after inhalation of long-acting beta 2-sympathomimetics could contribute to their therapeutical effects by antagonism with ACh on mAChR remains to be answered.

Adrenergic beta-Agonists↗
PubMed1977

Functional contribution of autonomic innervation to urethral striated sphincter: studies with parasympathomimetic, parasympatholytic and alpha-adrenergic blocking agents in spinal cord injury and control male subjects.

Mechanisms underlying urethral pressure changes at the external sphincter region after administration of neuropharmacologic agents were investigated with cystosphincterometric studies and electromyography of the external urethral sphincter in adult patients with spinal cord injury and control male subjects. Bethanechol chloride, propantheline or phentolamine were administered to 37 spinal cord injury men and 3 normal controls. After cystectomy 3 additional spinal cord injury patients were subjected to bethanechol studies. The results of these studies suggested that the pressure changes in the external sphincter zone were caused predominantly by the concurrent changes produced in the detrusor and/or the smooth muscle components of the proximal urethra and of the external sphincter zone.

Adolescent↗
PubMed1981

Different cystometric types of deficient micturition reflex control in female urinary incontinence with special reference to the effect of parasympatholytic treatment.

The effect of 4 weeks' treatment with emepronium bromide in 20 incontinent female patients with detrusor hyperreflexia was compared to the effect in 20 patients who did not have uninhibited detrusor contractions during filling cystometry but who were unable to suppress a voluntarily induced detrusor contraction. In both groups, 65% benefited from the drug and no statistically significant differences were seen in the decrease in frequency of voiding and incontinence episodes during treatment. There were no differences between the groups for age, type and degree of urinary incontinence, and radiological findings of bladder suspension defects. In these patients it is important to perform cystometry, including detrusor reflex activation procedures and the testing of their ability to suppress a voluntarily induced detrusor contraction.

Adult↗