1.
Mestranol (oestrogen) prolonged, whilst
lynestrenol (
progestin) reduced, the duration of
pentobarbitone and
hexobarbitone sleep in mice, whilst the effects of
barbitone were not altered.2. The effects of these
steroids on
pentobarbitone sleep were dose-related, did not show tachyphylaxis, and produced optimal effects after only 4 days pretreatment.3. The effects of
lynestrenol were abolished by SKF 525A, whilst those of
mestranol were markedly potentiated, suggesting a different mechanism and/or locus of action for
mestranol and SKF 525A.4. Examination of plasma levels of
pentobarbitone in mice pretreated with
mestranol,
lynestrenol or SKF 525A showed that
lynestrenol increased whilst
mestranol and SKF 525A reduced the rate of clearance of
barbiturate from the plasma.5. The effects of
lynestrenol disappeared when
pentobarbitone was prevented from inducing
hypothermia, whilst some significant prolongation of
pentobarbitone sleep persisted in
mestranol treated mice. This suggested that the ability to potentiate
hypothermia was not the sole mechanism by which the effects of
pentobarbitone were enhanced by
mestranol.6. It is concluded these
steroids alter the duration of action of
pentobarbitone (and
hexobarbitone) by changing the rate of
barbiturate metabolism. In the case of
mestranol, this might be a combination of an effect upon basal metabolic rate (enhancing
hypothermia) and a direct effect on the liver. An effect upon renal clearance cannot be excluded by these results.