α₁‐Adrenoceptors and muscarinic receptors in voiding function – binding characteristics of therapeutic agents in relation to the pharmacokinetics

Abstract

In vivo and ex vivo binding of a1-adrenoceptor and muscarinic receptors involved in voiding function is reviewed with therapeutic agents (a1-adrenoceptor antagonists: prazosin, tamsulosin and silodosin; and muscarinic receptor antagonists: oxybutynin, tolterodine, solifenacin, propiverine, imiafenacin and darifenacin) in lower urinary tract symptoms. This approach allows estimation of the inhibition of a well-characterized selective (standard) radioligand by unlabelled potential drugs or direct measurement of the distribution and receptor binding of a standard radioligand or radiolabelled form of a novel drug. In fact, these studies could be conducted in various tissues from animals pretreated with radioligands and/or unlabelled novel drugs, by conventional radioligand binding assay, radioactivity measurement, autoradiography and positron emission tomography. In vivo and ex vivo receptor binding with a1-adrenoceptor antagonists and muscarinic receptor antagonists have been proved to be useful in predicting the potency, organ selectivity and duration of action of drugs in relation to their pharmacokinetics. Such evaluations of drug-receptor binding reveal that adverse effects could be avoided by the use of new a1-adrenoceptor antagonists and muscarinic receptor antagonists for the treatment of lower urinary tract symptoms. Thus, the comparative analysis of a1-adrenoceptor and muscarinic receptor binding characteristics in the lower urinary tract and other tissues after systemic administration of therapeutic agents allows the rationale for their pharmacological characteristics from the integrated viewpoint of pharmacokinetics and pharmacodynamics. The current review emphasizes the usefulness of in vivo and ex vivo receptor binding in the discovery and development of novel drugs for the treatment of not only urinary dysfunction but also other disorders.

Use of Silodosin to Visualize the Posterior Urethra in Pelvic Floor Urethral Distraction Defect Patients

“…Silodosin is associated with a low incidence of side effects (e.g. orthostatic hypotension and retrograde ejaculation) due to its selective action ( 7 , 8 ). The ingestion of a single dose of silodosin led to a statistically significant increase in the bladder neck opening in our study.…”

La polipharmacy nel paziente con infezione da HIV: l’esperienza dell’ambulatorio GAP.

“…In particolare, questi pazienti assumevano inibitori dell'enzima di conversione dell'angiotensina (n = 6), beta-bloccanti (n = 5), diuretici (n = 4), antagonisti del recettore dell'angiotensina (n = 2) e/o calcio antagonisti (n = 2). La discrepanza tra le interazioni previste e l'esito clinico può essere correlata o all'ampio indice terapeutico degli alfa1-bloccanti e/o alla mancanza di chiare correlazioni tra le concentrazioni plasmatiche di questi farmaci e i loro effetti emodinamici (21)(22)(23). In realtà, sebbene la farmacocinetica di questi farmaci sia stata ben caratterizzata, la loro associazione con gli effetti ipotensivi è ancora poco definita.…”

Effect of alpha1-blockers on stentless ureteroscopic lithotripsy

“…Alpha1-blocker is considered to be a safe and effective treatment for the small lower ureteral calculi. It was reported that alpha1-adrenergic receptors are the most abundant receptors in ureteral smooth muscle cells and it could mimic the stent-related symptoms and the lower urinary tract symptoms due to benign prostatic hyperplasia ( 6 ). To avoid the stent-associated complications, therefore, an investigation with respect to the possibility of using alpha1-blocker for the purpose of stentless ureteroscopic lithotripsy is necessary.…”