THE ANTIDIURETIC ACTION OF BARBITURATES (PHENOBARBITAL, AMYTAL, PENTOBARBITAL) AND THE MECHANISM INVOLVED IN THIS ACTION

¹ Department of Pharmacology, New York University College of Medicine

1. Normal dogs, in the postabsorptive state and in water equilibrium, excreted ingested water (40 cc./kgm.) or intravenously infused water (25 cc./kgm.) almost quantitatively within three hours.

2. Phenobarbital sodium given intravenously in one-half of the anesthetic dose (0.04 gram/kgm.), either 40 minutes after the administration of water by stomach or a few minutes before the intravenous infusion of water was started, inhibited water diuresis in every normal dog studied. The degree of this inhibition was such that the water output during the experimental period was about one-half of the water intake. Phenobarbital in doses smaller than 0.035-0.040 gram/kgm. had no consistent effect on water diuresis.

3. Phenobarbital sodium given intravenously in full anesthetic doses (0.08 gram/kgm.) inhibited water diuresis in normal dogs to a degree not more marked than that produced by the half anesthetic dose.

4. Still larger doses of phenobarbital sodium, causing very deep anesthesia, inhibited water diuresis to a greater degree in normal dogs.

5. In contrast to phenobarbital either amytal sodium or pentobarbital sodium, given intravenously in half anesthetic or even in full anesthetic doses, inhibited water excretion in only some animals. If an antidiuretic action was produced. by either dose of these drugs, it was about of the same degree as that produced by the smallest effective dose of phenobarbital.

6. The effect of repeated administrations of pentobarbital sodium on the water diuresis of an individual normal dog was in some cases the same, but not always so; for instance, dogs which failed to respond with an antidiuretic effect on the first or first and second occasions gave an antidiuretic response at a later time, whereas sometimes the first and third administrations produced an antidiuretic response and the second failed to do so.

7. In dogs in which the entire neurohypophysis (infundibular process,infundibular stem and median eminence) was destroyed and in which, as a result, permanent diabetes insipidus developed, the excretion of water was never inhibited by any of the barbiturates studied even when these drugs were given in full anesthetic doses.

8. In contrast to the above, in dogs in which the usual hypophysectomy was performed, leaving some parts of the neurohypophysis intact, as evidenced by only a transient diabetes insipidus followed by a permanent normal water balance, the barbiturates inhibited water diuresis.

9. Phenobarbital, amytal, and pentobarbital sodium then, inhibited water diuresis in dogs only if some part of the neurohypophysis was functioning.

10. In contrast to its effect on water diuresis in normal dogs, phenobarbital, even in full anesthetic doses, either did not inhibit saline diuresis (isotonic sodium sulfate solution) or inhibited it only in some animals (isotonic sodium chloride solution).

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