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Simple method of preparation and characterization of new antifungal active biginelli type heterocyclic compounds.


This study was completed by 163 patients. The IPSS-T, IPSS-S and quality of life index decreased significantly in both groups. An improved outcome (GRA ≥ 1) at 4 weeks was reported in 51/74 patients (68.9%) receiving doxazosin and 69/89 patients (77.5%) receiving tolterodine. The rate of improved outcome in patients with a TPV < 40 ml was significantly higher in tolterodine group (73.3% vs. 57.6%, p = 0.040). Patients with tolterodine treatment failure (GRA < 1) had higher baseline IPSS-V and IPSS intermittency domain, whereas patients with doxazosin treatment failure had a higher baseline IPSS urgency domain.

Interstitial cystitis is a condition with a poorly understood etiology and, consequently, various treatment options have been described in the literature, with a less than optimal outcome. The aim of this study was to examine the role of a combination of intravesical hydrocortisone and heparin, together with oral bladder sedatives and systemic triamcinolone, for the treatment of interstitial cystitis.

The aim of the present investigation was to evaluate the percutaneous absorption of tolterodine (TOL) using O-acylmenthol derivatives as enhancers as well as to correlate their enhancing activity under in vitro and in vivo conditions. The in vitro permeation studies of TOL were conducted in isopropyl myristate (IPM) solution or from patches in side-by-side diffusion cells. TOL pharmacokinetic parameters were determined after intravenous administration and topical application of patches without enhancer or with l-menthol and (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate (M-OA) as enhancers in rats. The in vitro permeation studies indicated that M-OA was the most promising enhancer for transdermal delivery, as 2-isopropyl-5-methylcyclohexyl 2-hydroxypanoate (M-LA) was merely effective in IPM solution. There was no significant difference between the control and l-menthol group in terms of the flux before patches were removed, while the skin reservoir effects of the enhancer-containing groups were significantly greater than that of the control group. The mean steady-state plasma concentrations after applying patches without enhancer or with l-menthol and M-OA as enhancers were 0.89, 0.84 and 1.47 microg/mL, respectively. The in vivo results observed from the three types of patches in rats were in good agreement with the plasma concentrations predicted from the in vitro data.

This prospective randomised comparative study included men aged ≥ 40 years with a total IPSS ≥ 8, IPSS storage subscore (IPSS-S) ≥ voiding subscore (IPSS-V) and PVR ≤ 250 ml. Subjects were randomised to receive tolterodine 4 mg or doxazosin 4 mg daily for 12 weeks. The primary end-point included changes of total IPSS, IPSS subscore and global response assessment (GRA) after treatment. The secondary end-points included comparisons of baseline parameters between patients with a GRA ≥ 1 and GRA < 1. All adverse events were also recorded.

Novel derivatives of Tolterodine (1) and Oxybutynin (2) have been designed using conformationally restricted azabicyclics as replacement for open-chain amines. The synthesis and structure-activity relationships are presented.

Bladder capacity at first sensation and maximum cystometric capacity increased significantly, by an average of 36.8mL (P=0.0402) and 82.3mL (P<0.0001), respectively. Maximum cystometric capacity increased by more than 50mL in 19 patients (49%) following treatment. Detrusor overactivity disappeared in three of 32 patients (9%), bladder capacity at first involuntary contraction increased significantly (P=0.0009), and amplitude of detrusor overactivity decreased significantly (P=0.0025). In patients with low-compliance bladder, bladder compliance increased significantly (P=0.0156). Overactive bladder symptom score, International Consultation on Incontinence Questionnaire-Short Form score, number of voids (per 24h and night-time), number of urgency episodes in 24h, number and amount of leaks in 24h, and amount of mean and maximum voided volumes all decreased significantly after treatment.

Endpoints included week 12 changes in bladder diary variables, IPSS scores, and safety variables.

Both the physiological role of muscarinic receptors for bladder function and the therapeutic efficacy of antimuscarinic agents for overactive bladder syndrome are well documented. We investigated the effect of antimuscarinic agents with different subtype selectivity on urodynamic parameters in nonhuman primates and rodents and compared plasma levels of these agents between species. Anesthetized rhesus monkeys were transurethrally catheterized, and the bladder was infused with saline. Urodynamic parameters were measured before and after intravenous drug administration. Tolterodine (nonselective) and oxybutynin (moderately M(3)-selective) increased bladder capacity at lower doses than those required to decrease micturition pressure. However, higher doses of darifenacin (M(3)-selective) were needed to increase the bladder capacity than those needed to decrease the micturition pressure. In rats, tolterodine had no effect on the bladder capacity but decreased the micturition pressure at all of the doses administered. Oxybutynin also decreased micturition pressure and increased bladder capacity at the highest dose. Plasma levels of these drugs overlap in both species. These results suggest that, in addition to the M(3) receptor, other muscarinic receptor subtypes contribute to regulate bladder storage function in nonhuman primates, since less subtype-selective tolterodine and oxybutynin showed higher specificity to the bladder capacity effect than the effect on micturition pressure compared with M(3)-selective darifenacin. In addition, the role of muscarinic receptors in bladder storage function varies between primates and rodents. Compared with rodents, muscarinic receptors may play a more active role during the storage phase to regulate the functional bladder capacity in primates.