Smooth Muscle

Druckman and Moore, Proceedings of the Society for Experimental Biology and Medicine (1955), 465 studied the effect of PHT on isolated rabbit intestine smooth muscle contractions. PHT (60-80 µg/ml) decreased the amplitude of contractions. The authors state that this direct effect of PHT on intestinal smooth muscle, in addition to its stabilizing effect on the central nervous system, is relevant to its use in the treatment of clinical conditions of intestinal hypermotility and spasticity.

465. Druckman, R. and Moore, F. J., Effects of sodium diphenylhydantoinate upon isolated small intestine of the rabbit, Proc. Soc. Exp. Biol. Med., 90: 173-176, 1955.

Khan and McEwen, Proceedings of the Canadian Federation of Biological Societies (1967), 192 studied the effect of PHT and 5,5-diphenyl-2-thiohydantoin (DTH) on the activity of isolated uterine tissue from the albino rat. PHT and DTH decreased the rate and amplitude of contractions. To attain complete relaxation PHT was required in a concentration of 33 µg/ml, and for DTH, 17 µg/ml was required.

192. Khan, M. T. and McEwen, H. D., Effect of diphenylhydantoins on rat uterus in vitro, Proc. Can. Fed. Biol. Soc., 10: 161, 1967.

Woodbury and Kemp, Psychiatria, Neurologia, Neurochirurgia (1971),1696 showed that PHT tended to reduce toward normal the amplitude of contraction of the smooth muscle of rat ileum when it had been rendered hyperexcitable by barium ions. Other work from their laboratory showed that small amounts of PHT in-creased the release of acetylcholine from parasympathetic nerve endings in the wall of rat ileum and also from intramural ganglia, thus stimulating contraction of the ileum. However, when contraction of the ileum was made excessive by the addition of acetylcholine, PHT inhibited the excessive contractions. The authors refer to this selective action of PHT as a biphasic effect.

1696. Woodbury, D. M. and Kemp, J. W., Pharmacology and mechanisms of action of diphenylhydantoin, Psychial. Neurol. Neurochir., 74: 91-115, 1971.

Chou, Kuiper and Hsieh, Gastroenterology (1972), 899 noting that PHT has been used in the treatment of spastic colon, studied the effects of PHT on phasic motor activity and contractile state of an in situ segment of the ascending colon and terminal ileum of dog. PHT decreased the contractile state of both ileum and colon, making them more distensible, and also decreased the phasic activity of the colon.

899. Chou, C. C., Kuiper, D. H., and Hsieh, C. P., Effects of diphenylhydantoin on motility and compliance of the canine ileum and colon, Gastroenterology, 62: 734, 1972.

Ferrari and Furlanut, Archives Internationales de Pharmacodynamie et de Therapie (1973), 1021 studied the effect of PHT on the mechanical and electrical activity of the isolated guinea pig ileum preparations. PHT enhanced muscular relaxation and regulated the response of smooth muscle to acetylcholine stimulation. The authors note that these effects are consonant with PHT's stabilization of excitable membranes.

1021. Ferrari, M. and Furlanut, M., Effects of diphenylhydantoin on smooth muscle, Arch. Int. Pharmacodyn., 203: 101-106, 1973.

Vanasin, Bass, Mendeloff and Schuster, American Journal of Digestive Diseases (1973), 1644 studied the direct effect of PHT on isolated strips of smooth muscle of colon from fourteen humans and twenty-four dogs. Whether stimulated with acetylcholine, 5-hydroxytryptamine, or electrically, PHT significantly increased relaxation time and decreased contraction time, compared to controls. The authors conclude that PHT can act directly on smooth muscle, as well as on neuromuscular junctions, and that their observations suggest a basis for the therapeutic use of PHT in the treatment of spastic colon syndrome. (See also Refs. 2380, 2437.)

1644. Vanasin, B., Bass, D. D., Mendeloff, A. I., and Schuster, M. M., Alteration of electrical and motor activity of human and dog rectum by diphenylhydantoin, Amer. J. Dig. Dis., 18: 403-410, 1973.

2380. Chadda, V. S., Joshi, K. G., Chadda, S., A double-blind crossover study of diphenylhydantoin in irritable bowel syndrome, J. Assoc. Physicians India, 31 (7): 425-7, 1983.
2437. De la Torre, R., Navarro, J. L., Aldrete, J. A., Comparison between phenytoin and conventional treatment for irritable bowel syndrome, Curr. Ther. Res., 38(4): 661-9, 1985.

Melacini, Furlanut, Ferrari and Volta, Archives Internationales de Pharmacodynamie et de Therapie (1975), 1978 demonstrated that PHT counteracts repetitive discharge under sustained depolarization of guinea pig taenia coli, yet does not affect normal membrane resistance.

1978. Melacini, P., Furlanut, M., Ferrari, M. and Volta, S. D., Effects of quinidine and diphenylhydantoin on membrane resistance in smooth muscle, Arch. Int. Pharmacodyn., 213(1): 17-21, 1975.

Khan, Archives Internationales de Pharmacodynamie et de Therapie (1982), 2660 found that PHT (7.5-120 µM) and diphenylthiohydantoin inhibited spontaneous motility of rat uterus in a dose-dependent manner. PHT reduced the stimulatory effects of ouabain, acetylcholine, oxytocin, ATP and prostaglandins 12 and E2 and increased the inhibitory effects of theophylline and nitroglycerin.

2660. Khan, M. T., Studies on the uterine inhibitory actions of diphenylhydantoins, Arch. Int. Pharmacodyn. Ther., 260: 265-73,1982.

Calixto and De-Lima, Brazilian Journal of Medical and Biological Research (1983), 2375 reported that PHT caused a dose-dependent, noncompetitive inhibition of the contractions induced by norepinephrine, acetylcholine and serotonin in isolated rat vas deferens. PHT also antagonized calcium-induced contractions of the depolarized vas deferens in a competitive manner. The authors suggest that PHT achieves its therapeutic effect, at least in part, by reducing calcium influx in excitable membranes.

2375. Calixto, J. B., De-Lima, T. C., Diphenylhydantoin inhibition of drug-induced contractions of isolated rat vas deferens: additional evidence for a calcium-blocking action, Braz. J. Med. Biol. Res., 16: 327-31, 1983.