piperidines and Urination-Disorders

Topics: Aged; Aged, 80 and over; Amantadine; Cerebral Infarction; Cholinergic Antagonists; Cognition Disorders; Deamino Arginine Vasopressin; Diagnosis, Differential; Donepezil; Humans; Indans; Levodopa; Piperidines; Quality of Life; Serotonin Agents; Urination Disorders

Topics: Acetylcholine; Adult; Aged; Aged, 80 and over; Cisapride; Digestive System; Female; Humans; Male; Middle Aged; Piperidines; Retrospective Studies; Urination Disorders

Topics: Clinical Trials as Topic; Depression, Chemical; Flavonoids; Humans; Muscle Contraction; Muscle, Smooth; Parasympatholytics; Piperidines; Propantheline; Stimulation, Chemical; Urinary Bladder; Urinary Bladder, Neurogenic; Urination; Urination Disorders

With the aim of improving of the efficacy and decreasing the side effects of oxybutynin (1), N-[(tetrahydro-3- or 4-pyridyl)methyl]-, N-(4-piperidyl)-, and N-(3- or 4-piperidylalkyl)-2-hydroxyacetamides (3a-n, 4a-g) and the related carboxamides (3o-r, 4h-k, 13', 17) were synthesized and evaluated for inhibitory activity against urinary bladder rhythmic contraction in rats and for mydriatic activity in rats. Some of these compounds were superior to oxybutynin in both inhibitory activity against bladder contraction and selectivity between inhibitory activity against bladder contraction and mydriatic activity. Among them, N-[(1,2,3,6-tetrahydro-4-pyridyl)methyl]- and N-[(1,2,3,6-tetrahydro-1-methyl-4-pyridyl)methyl]-2-hydroxy-2,2- diphenylacetamide (3e, 3f) exhibited the most potent inhibitory activity against bladder contraction (ED30 = 0.005 and 0.003 mg/kg i.v., respectively). Judging from the effect of 3e on detrusor contraction in vitro in guinea-pigs, it appeared that the inhibitory activity of 3e against bladder contraction in vivo was related mainly to its inhibitory activity against detrusor contraction in vitro induced with carbachol (antimuscarine-like activity). The selectivity (20-fold) of 3e between inhibitory activity against bladder contraction and mydriatic activity was greatly superior to that (0.48-fold) of oxybutynin. Compound 3e was synthesized by debenzylation (method E or F) of the corresponding N-[[1-(4-methoxybenzyl)-tetrahydro-4-pyridyl]methyl] derivative (3k), which was prepared by acylation (method B) of the corresponding (tetrahydro-4-pyridyl)methylamine (7k) or by reduction (method D) of the corresponding pyridinium chloride (14k) with NaBH4.

Topics: Acetamides; Animals; In Vitro Techniques; Mandelic Acids; Muscle Contraction; Muscle, Smooth; Mydriasis; Piperidines; Rats; Urinary Bladder; Urination Disorders

Topics: Adult; Aged; Cisapride; Female; Humans; Male; Middle Aged; Piperidines; Urination Disorders

The effects of FL-155, which was synthesized to develop a new orally-active anti-pollakiuria agent, on the rhythmic bladder contractions were studied in anesthetized rats. At a pressure exceeding 10 cm H2O in the bladder, a rhythmic bladder contraction was observed up to at least 120 min. This response was abolished by a spinal (C1 level) cut, cuts of both pelvic nerves, thiopental (3.0 mg/kg, i.v.) or lidocaine (1.0 mg/kg, i.v.); and atropine (0.01 mg/kg, i.v.) strongly inhibited the amplitude of the response. FL-155 and flavoxate, in intravenous (0.3-3.0 mg/kg and 1.0-3.0 mg/kg, respectively) and intraduodenal (12.5-100 mg/kg and 200-400 mg/kg, respectively) administrations, dose-dependently abolished the rhythmic bladder contractions, and FL-155 was 8-16 times more potent than flavoxate in intraduodenal administrations. These results suggest that the rhythmic bladder contraction in anesthetized rat may be a polysynaptic reflex through pelvic nerves and the central nervous system (supraspinal level), and FL-155 appears to be a candidate for an orally active anti-pollakiuria agent.

Topics: Animals; Atropine; Flavoxate; Lidocaine; Male; Periodicity; Piperidines; Rats; Rats, Inbred Strains; Reflex; Thiopental; Urinary Bladder; Urination Disorders

Topics: Flavonoids; Humans; Muscle, Smooth; Parasympatholytics; Piperidines; Urinary Bladder; Urination Disorders