Hostname: page-component-7bb8b95d7b-495rp Total loading time: 0 Render date: 2024-10-06T03:43:01.411Z Has data issue: false hasContentIssue false

Physiological and pharmacological basis for the chemotherapy of enuresis1

Published online by Cambridge University Press:  09 July 2009

J. D. Stephenson*
Affiliation:
Department of Pharmacology, Institute of Psychiatry, London
*
2Address for correspondence: Dr J. D. Stephenson, Department of Pharmacology, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF.

Synopsis

Enuresis is a disorder of micturition occurring in the absence of an organic urinary tract lesion. To understand its possible causation, the mechanisms controlling micturition are described together with the possible sites of action of various anti-enuretic agents, particularly imipramine. It is concluded that further research into the central control of micturition is required before the precise actions of centrally-acting anti-enuretic agents can be elucidated. Knowledge of these may give insight into the nature of the defect causing enuresis.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1979

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

1

This article formed the basis of a lecture given at the Institute of Psychiatry, London, October 1977.

References

Awad, S. A., Bruce, A. W., Carro-Ciampi, G., Downie, J. W., Lin, M. & Marks, G. S. (1974). Distribution of α-and β-adrenoceptors in human urinary bladder. British Journal of Pharmacology 50, 525529.CrossRefGoogle ScholarPubMed
Barrington, F. J. F. (1931). The component reflexes of micturition in the cat. Brain 54, 177189.CrossRefGoogle Scholar
Blackwell, B. & Currah, J. (1973). The psychopharmacology of nocturnal enuresis. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 231257. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Boston, L. N. (1928). Dysuria following ephedrine therapy. Medical Times 56, 94.Google Scholar
Brindley, G. S. & Craggs, M. D. (1975). The effect of atropine on the urinary bladder of the baboon and of man. Journal of Physiology (London) 256, 55P.Google Scholar
Buttarazzi, P. J. (1977). Oxybutynin chloride (Ditropan) in enuresis. Journal of Urology 118, 46.Google Scholar
Caine, M. (1977). The importance of adrenergic receptors in disorders of micturition. European Urology 3, 16.CrossRefGoogle ScholarPubMed
Caine, M., Pfau, A. & Perlberg, S. (1976). The use of α-adrenergic blockers in benign prostatic obstruction. British Journal of Urology 48, 255263.Google Scholar
Callingham, B. A. (1966). The effects of imipramine and related compounds on the uptake of noradrenaline into sympathetic nerve endings.In Anti-depressant Drugs. Proceedings of the 1st International Symposium. (ed. Garratini, S. and Dukes, M.), pp. 3543. Elsevier: Amsterdam.Google Scholar
Craggs, M. D. & Stephenson, J. D. (1979). The involvement of the sympathetic nervous system in micturition, including reference to the use of imipramine in enuresis. Catecholamnines: Basic and Clinical Frontiers (ed. Usdin, E.). Pergamon Press: New York (in the press).Google Scholar
De Groat, W. C. & Lalley, P. M. (1972). Reflex firing in the lumbar sympathetic outflow to activation of vesical afferent fibres. Journal of Physiology (London) 226, 289309.CrossRefGoogle ScholarPubMed
De Groat, W. C. & Saum, W. R. (1972). Sympathetic inhibition of the urinary bladder and of pelvic ganglionic transmission in the cat. Journal of Physiology (London) 220, 297314.Google Scholar
De Sy, W., Lacroix, E. & Leusen, I. (1974). An analysis of the urinary bladder response to hypogastric nerve stimulation in the cat. Investigative Urology 11, 508515.Google Scholar
Denny-Brown, D. & Robertson, E. G. (1933). On the physiology of micturition. Brain 56, 149190.CrossRefGoogle Scholar
Dimson, S. B. (1977). Desmopressin as a treatment for enuresis. Lancet i, 1260.CrossRefGoogle Scholar
Diokno, A. C., Hyndman, C. W., Hardy, D. A. & Lapides, J. (1972). Comparison of action of imipramine (Tofranil) and propantheline (Probanthine) on detrusor contraction. Journal of Urology 107, 4243.CrossRefGoogle ScholarPubMed
Douglas, J. W. B. (1973). Early disturbing events and later enuresis. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 137151. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Doyle, P. T. & Briscoe, C. E. (1976). The effects of drugs and anaesthetic agents on the urinary bladder and sphincters. British Journal of Urology 48, 329335.Google Scholar
Dröes, J. T. P. M. (1974). Observations on the musculature of the urinary bladder and the urethra in the human foetus. British Journal of Urology 46, 179185.CrossRefGoogle ScholarPubMed
Edvardsen, P. (1968). Nervous control of urinary bladder in cats. The expulsion phase. Acta Physiologia Scandinavica 72, 172182.Google Scholar
Edvardsen, P. (1972). Neurophysiological aspects of enuresis. Acta Neurologica Scandinavica 48, 222230.Google Scholar
Edvardsen, P. & Setekleiv, J. (1968). Distribution of adrenergic receptors in the urinary bladder of cats, rabbits and guinea pigs. Acta Pharmacologica et Toxicologica 26, 437445.CrossRefGoogle ScholarPubMed
Edvardsen, P. & Ursin, H. (1968). Micturition threshold in Cats with amygdala lesions. Experimnental Neurology 21, 495501.CrossRefGoogle ScholarPubMed
Elbadawi, A. & Schenck, E. A. (1968). A new theory of the innervation of bladder musculature. Part 1. Morphology of the intrinsic vesical innervation apparatus. Journal of Urology 99, 585587.Google Scholar
Elbadawi, A. & Schenck, E. A. (1971). A new theory of the innervation of bladder musculature. Part 3. Postganglionic synapses in uretero-vesico-urethral autonomic pathways. Journal of Urology 105, 372374.CrossRefGoogle Scholar
Elliott, T. R. (1907). The innervation of the bladder and urethra. Journal of Physiology (London) 35, 367445.CrossRefGoogle ScholarPubMed
Forsythe, W. I. & Redmond, A. (1974). Enuresis and spontaneous cure rate: study of 1129 enuretics. Archives of Disease in Childhood 49, 259263.CrossRefGoogle Scholar
Garry, R. C., Roberts, R. D. M. & Todd, J. K. (1959). Reflexes involving the external urethral sphincter in the cat. Journal of Physiology (London) 149, 653665.Google Scholar
General Practitioner Research Group (1970). Sedatives and stimulants compared in enuresis. Practitioner 204, 584586.Google Scholar
Glidden, R. S. & Di Bonna, F. J. (1977). Urinary retention associated with ephedrine. Journal of Pediatrics 90, 10131014.Google Scholar
Gosling, J. A. & Dixon, J. S. (1975). The structure and innervation of smooth muscle in the wall of the bladder neck and proximal urethra. British Journal of Urology 47, 549558.CrossRefGoogle ScholarPubMed
Gosling, J. A., Dixon, J. S. & Lendon, R. G. (1977). The autonomic innervation of the human male and female bladder neck and proximal urethra. Journal of Urology 118, 302305.Google Scholar
Gururaj, V. J., Reddy, H. V., Russo, R. M. & Allen, J. E. (1975). Flavoxate hydrochloride in the treatment of Childhood enuresis. Clinical Medicine 06, 2527.Google Scholar
Guttin, I. J. (1964). Tratamiento de la enuresis nocturna infantil con diazepoxide. Presentación de 50 casos clinicos. Revista Medicina 44, 579.Google Scholar
Hägglund, T. B. & Parkkulainen, K. V. (1964). Enuretic children treated with imipramine (Tofranil). A cystometric study. Annales Paediatriae Fenniae 11, 5359.Google Scholar
von Harrer, G. (1961). Imipramin und Wasserhaushalt. Medicina Experimentalis (Basel) 5, 285290.Google Scholar
Hertting, G., Axelrod, J. & Whitby, L. G. (1961). Effect of drugs on the uptake and metabolism of 3H-norcpinephrine. Journal of Pharmacology and Eperimental Therapeutics 134, 146153.Google Scholar
Hutch, J. A. (1972). Anatomy and Physiology of the Bladder, Trigone and Urethra. Butterworths: London.Google Scholar
Hutch, J. A. & Shopfner, C. E. (1968). A new theory of the anatomy of the internal urinary sphincter and the physiology of micturition. VI. The base plate and enuresis. Journal of Urology 99, 174177.Google Scholar
Iggo, A. (1955). Tension receptors in the stomach and urinary bladder. Journal of Physiology (London) 128, 593607.Google Scholar
Jones, K. S. & Tibbetts, M. A. (1959). Pituitary snuff, propantheline and placebos in the treatment of enuresis. Journal of Mental Science 105, 371381.Google Scholar
Kales, A., Kales, J. D., Jacobson, A., Humphrey, F. J. & Soldatos, C. R. (1977). Effects of imipramine on enuretic frequency and sleep stages. Pediatrics 60, 431436.Google Scholar
Khanna, O. P. (1976). Disorders of micturition. Neuropharmacologic basis and results of drug therapy. Urology 8, 316328.CrossRefGoogle ScholarPubMed
Kline, A. H. (1968). Diazepam and the management of nocturnal enuresis. Clinical Medicine 12, 2022.Google Scholar
Krane, R. J. & Olsson, C. A. (1973 a). Phenoxybenzamine in neurogenic bladder dysfunction. I. A theory of micturition. Journal of Urology 110, 650652.Google Scholar
Krane, R. J. & Olsson, C. A. (1973 b). Phenoxybenzamine in neurogenic bladder dysfunction. Clinical considerations. Journal of Urology 110, 653656.Google Scholar
Lake, B. (1975). Alprenolol and enuresis. Medical Journal of Australia 1, 367.Google ScholarPubMed
Langley, J. N. & Anderson, H. K. (1895). The innervation of the pelvic and adjoining viscera. Part II. The bladder. Journal of Physiology (London) 19, 7184.Google Scholar
Lapides, J., Hodgson, N. B., Boyd, R. E., Shook, E. L. & Lichtwardt, J. R. (1958). Further observations on pharmacologic reactions of the bladder. Journal of Urology 79, 707713.Google Scholar
Learmonth, J. R. (1931). A contribution to the neurophysiology of the urinary bladder in man. Brain 54, 147176.Google Scholar
LeCompte, S. & Orval, J. (1965). Analyse de l'action de chlordiazepoxide (Librium) sur le comportement des enfants. Acta Paedopsychiatrica (Basel) 32, 90106.Google Scholar
MacKeith, R. C. (1972). Is maturation delay a frequent factor in the origins of primary nocturnal enuresis? Developmental Medicine and Child Neurology 14, 217223.Google Scholar
Mahony, D. T., Laferte, R. O. & Mahoney, J. E. (1973). Part VI. Observations on sphincter-augmenting effect of imipramine in children with urinary incontinence. Urology 1, 317323.Google Scholar
Mahony, D. T., Laferte, R. O. & Blais, D. J. (1977). Integral storage and voiding reflexes. Neurophysiologic concept of continence and micturition. Urology 9, 95106.Google Scholar
McNeal, J. E. (1972). The prostate and prostatic urethra: a morphologic synthesis. Journal of Urology 107, 10081016.CrossRefGoogle ScholarPubMed
Miller, F. J. W., Court, S. D. M., Walton, W. S. & Knox, E. G. (1960). Growing up in Newcastle-upon-Tyne. Oxford University Press: London.Google Scholar
Muellner, S. R. (1958). The voluntary control of micturition in man. Journal of Urology 80, 473478.Google Scholar
Nergadh, A. & Boreus, L. O. (1972). Autonomic receptor function in the lower urinary tract of man and cat. Scandinavian Journal of Urology and Nephrology 6, 3236.Google Scholar
Noack, C. H. (1964). Enuresis nocturna: a long term study of 44 children treated with imipramine hydrochloride (Tofranil) and other drugs. Medical Journal of Australia 1, 191192.CrossRefGoogle ScholarPubMed
Norlén, L., Dahlström, A., Sundin, T. & Svedmyr, N. (1976). The adrenergic innervation and adrenergic receptor activity of the feline urinary bladder and urethra in the normal state and after hypogastric and/or parasympathetic denervation. Scandinavian Journal of Urology and Nephrology 10, 177184.Google Scholar
Oswald, I. (1968). Drugs and sleep. Pharmacological Reviews 20, 273303.Google ScholarPubMed
Raezer, D. M., Wein, A. J., Jacobowitz, D. & Corriere, J. N. (1973). Autonomic innervation of canine urinary bladder. Urology 2, 211221.Google Scholar
Raz, S., Zeigler, M. & Caine, M. (1972). The vascular component in the production of intraurethral pressure. Journal of Urology 108, 9396.Google Scholar
Raz, S., Kaufman, J. J., Ellison, G. W. & Mayers, L. W. (1977). Methyldopa in treatment of neurogenic bladder disorders. Urology 9, 188190.Google Scholar
Rehavi, M., Maayani, S. & Sokolovsky, M. (1977). Tricyclic antidepressants as antimuscarinic drugs: in vivo and in vitro studies. Biochemical Pharmacology 26, 15591567.CrossRefGoogle ScholarPubMed
Ritvo, E. R., Ornitz, E. M., Gottlieb, F., Poussaint, A. R., Maron, B. J., Ditman, K. S. & Blinn, K. A. (1969). Arousal and non-arousal enuretic events. American Journal of Psychiatry 126, 7784.CrossRefGoogle Scholar
Roy, P. B., Mercure, J., Lebel, G. & Bourque, R. (1963). Contribution à l'étude de ‘Librium’ dans le traitement des alcoholiques. Union Medicate du Canada (Montreal) 92, 218220.Google Scholar
Ruch, T. C. (1960). Central control of the bladder. In Handbook of Physiology, Section 1. Neurophysiology, vol. 2 (ed. Field, J., Magoun, H. W. and Hall, V. E.), pp. 12071223. Williams & Wilkins: Baltimore.Google Scholar
Rutter, M. (1973). Indications for Research. III. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 292300. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Rutter, M. L., Yule, W. & Graham, P. J. (1973). Enuresis and behavioural deviance: some epidemiological considerations. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 137151. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Salmon, M. A. (1973). The concept of day-time treatment for primary nocturnal enuresis. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 189194. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Shaffer, D. (1973). The association between enuresis and emotional disorder: a review of the literature. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 118135. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Shaffer, D., Hedge, B. & Stephenson, J. D. (1978). Trial of an alpha-adrenolytic drug (Indoramin) for nocturnal enuresis. Developmental Medicine and Child Neurology 20, 183188.Google Scholar
Shaffer, D., Stephenson, J. D. & Thomas, D. V. (1979). Some effects of imipramine on micturition and their relevance to its anti-enuretic activity. Neuropharmacology 18, 3337.Google Scholar
Sigg, E. B. (1959). Pharmacological studies with Tofranil. Canadian Psychiatrists' Association Journal 4 (Suppl.), 7585.Google Scholar
Sigg, E. B. & Sigg, T. D. (1964). Sympathetic stimulation and blockade of the urinary bladder in cat. International Journal of Neuropharmacology 3, 241251.Google Scholar
Stanton, S. L. (1978). Diseases of the urinary system. Drugs acting on the bladder and urethra. British Medical Journal i, 16071608.Google Scholar
Starfield, S. B. (1967). Functional bladder capacity in enuretic and non-enuretic children. Journal of Pediatrics 70, 777781.CrossRefGoogle Scholar
Taira, N. (1972). The autonomic pharmacology of the bladder. Annual Reviews in Pharmacology 12, 197208.Google Scholar
Tanagho, E. A. & Smith, D. R. (1966). The anatomy and function of the bladder neck. British Journal of Urology 38, 5471.CrossRefGoogle ScholarPubMed
Thompson, I. M. & Lauvetz, R. (1976). Oxybutynin in bladder spasm, neurogenic bladder and enuresis. Urology 8, 452454.Google Scholar
Troup, C. W. & Hodgson, N. B. (1971). Nocturnal functional bladder capacity in enuretic children. Journal of Urology 105, 129132.Google Scholar
Tulloch, A. G. S. (1974). The vascular contribution to intraurethral pressure. British Journal of Urology 46, 659664.Google Scholar
Wallace, I. R. & Forsyth, W. I. (1969). The treatment of enuresis. A controlled clinical trial of propantheline, propantheline and phenobarbitone and a placebo. British Journal of Clinical Practice 23, 207210.Google Scholar
Werry, J. S., Aman, M. G., Dowrick, P. & Lampen, E. L. (1977). Imipramine and chlorodiazepoxide in enuresis. Psychopharmacology Bulletin 13, 3839.Google Scholar
Whitfield, H. N., Doyle, P. T., Mayo, M. E. & Poopalasingham, N. (1976). The effect of adrenergic blocking agents on outflow resistance. British Journal of Urology 47, 823827.Google Scholar
Winter, D. L. (1971). Receptor characteristics and conduction velocities in bladder afferents. Journal of Psychiatric Research 8, 225235.Google Scholar
Woodburne, R. T. (1960). Structure and function of the urinary bladder. Journal of Urology 84, 7985.CrossRefGoogle Scholar
Yeates, W. K. (1973). Bladder function: increased frequency and nocturnal incontinence. In Bladder Control and Enuresis (ed. Kolvin, I., MacKeith, R. and Meadow, S. R.), pp. 151155. SIMP Clinics in Developmental Medicine 48/49. Heinemann: London.Google Scholar
Yeates, W. K. (1974). Neurophysiology of the bladder. Paraplegia 12, 7382.Google Scholar