The Pharmacology of Micturition. The Effect of Drugs on the Bladder and Urethra with Autonomic Supply Intact

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Abstract
Winter investigated the effects upon the activity of the bladder and urethra of drugs acting on the parasympathetic, sympathetic, and central nervous systems and on smooth muscle. Unanesthe-tized dogs were used and the bladder capacity, urethral resistance and bladder irritability were determined. Bilateral removal of a section of the pudendal nerves was performed on all dogs in order to exclude changes resulting from voluntary efforts to withhold micturition. The drugs were dissolved in sufficient distilled water to make the vol. injected 0.1 cc./kg. All drugs were given subcut. except paraldehyde, which was given by rectal catheter, and theophylline, which was given intramusc. Of the parasympathomimetic drugs, acetylcholine and acetylbetamethyl-choline reduced urethral resistance, but carbaminolylcholine, the urethane of betamethylcholine, and pilocarpine caused a definite increase in urethral resistance. Of the parasympathetic "blocking" drugs, scopolamine hydrochloride (0.1 mg./kg.) and atropine in doses large enough to produce excitement tended to cause increased irritability, decreased urethral resistance and decreased capacity. Choline esterase inhibitors, such as physostigmine sulfate in doses of 0.1 mg./kg. produced increased irritability and urethral resistance; prostigmine methylsulfate in doses of 0.075 mg./kg. caused very little effect, although a slight decrease in capacity was the rule. In addition to their bladder effects, both drugs produced fibrillation of the voluntary muscles. Morphine in a dosage of 2.0 mg./kg. resulted in increased irritability, decreased urethral resistance and decreased capacity; in doses of 1.0 mg./kg. the increased irritability was not evident. Prostigmine potentiated the effects of morphine. Epinephrine hydrochloride even in doses as large as 2.0 mg./kg. failed to act upon the bladder. Neosynephrine in similar doses caused a marked rise in urethral resistance and a definite increase in bladder irritability with a resultant decrease in capacity. Cobefrine (2.0 mg./kg.) tended to cause a decrease in irritability and decrease in urethral resistance. Benzedrine and ephedrine, in doses of 5 and 10 mg./kg., resp., raised the urethral resistance and tended to reduce bladder irritability. Of the drugs stimulating the C. N. S., strychnine (0.1 mg./kg.) produced no change in bladder activity; metrazol (20 mg./kg.) increased bladder irritability in some instances. Caffeine with Na benzoate (30 mg./kg.) raised urethral resistance, reduced irritability of bladder and increased its capacity. C. N. S. depressants, such as Na pentobarbital (10 mg/kg.) and paraldehyde (0.9 cc./kg.), caused reduced urethral resistance and reduced capacity. Drugs stimulating directly smooth muscle, such as posterior pituitary soln. and BaCl2 (1.0 mg./kg.), caused increased bladder irritability, decreased capacity, and decreased urethral resistance. Smooth muscle depressants, such as theophylline with monoethanolamine (30 mg./kg.), papaverine hydrochloride (12.5 mg./kg.) and Na nitrite (10 mg./kg.) reduced urethral resistance. An outline of the mechanism of drug action on the bladder and urethra is presented.