In cold-stressed rats,11 IVa and j and V did not decrease peripheral plasma corticosterone levels at oral doses which exceeded those used to induce a natriuretic response (100 mg/kg).14 However, in rats, V caused adrenal hypertrophy, decreased male sex accessory organ weights, and decreased the rate of gain in body weight. These effects have not been observed with IVa and j.Earlier studies1•'2 had established that VI possessed a highly desirable spectrum of activity in natriuretic and adrenal corticosteroid inhibition assays. It caused marked natriuresis in Na+-depleted rats (a finding conil l) W. A. Zuccarello and G. J. Frishmuth, unpublished observations. sisteut with, but not. proof of, aldosterone inhibition) at oral doses which did not suppress peripheral plasma, corticosterone levels.1 In vitro findings supported the in vivo observations.1/2 Among (lie natriuretic agents tested in our laboratories, VI liad been the most potent of those which appeared to act by selectively inhibiting aldosterone biosynthesis.14 In the present series of compounds, both IVa. and j liad the same desirable biological selectivity as VI but were more active. In comparative studies, it was shown that VI was about two to three times as potent as VII. In turn, IVa. was about• twice as potent as XT, and IVj was about twice as potent as IVa (about four times as potent• as XT, and about eight to twelve times as potent as VII).14 The biological activity of IVj will be described in greater detail elsewhere.

No abstract

In the unanesthetized spinal cat at normotensive levels the crossed extensor reflex appeared considerably more variable than the patellar reflex. Both reflexes failed progressively as blood pressure was lowered but became hyperexcitable and were accompanied by convulsions at mean arterial pressures of 20–40 mm Hg. The crossed extensor reflex was more affected by hypotension than the patellar reflex. These reflexes disappeared under continued severe hypotension and recovered upon restoration of blood pressure to normal. Supplementary observations on spinal and intact cats under chloralose anesthesia indicated that the patellar reflex was more affected at less severe hypotensive levels in animals with an intact cerebrospinal axis.

The construction of an activity-measuring device that utilizes a nutating annular animal enclosure is described. The instrument converts motor activity to numerical scores. With mice, the logarithms of these scores assume a normal distribution. A second test occurring 1 day, week, or month after the first fails to exhibit any habituation of the animals.

analyses are indicated only by symbols of the elements, analytical results for those elements were within ±0.4% of the theoretical values.( + )-3-Methoxy-6a-hydroxy-4,5a-epoxy-A7-A'-methylisomorphinan (írans-Codeine) (II).-A mixture of I (2.8 g), AcOK (7 g), HaO (2 ml), and DMF (40 ml) was refluxed for 23 hr and evaporated in vacuo.The residue was dissolved in H20, basified with , , extracted with CHCls, dried, and evaporated. Conversion of the residue into the picrate in EtOH gave II picrate (1.26 g, 53.2%), mp [244][245]. This was identical with an authentic sample.3-Methoxy-6-oxo-4,5a-epoxy-Ar-methyIisomorphinan (trans-Dihydrocodeinone) (IV) Picrate.-A mixture of III (from 0.35 g of the hydrochloride), Al(0-<-Bu)3 (0.35 g), benzophenone (1.7 g), and C6H6 (5 ml) was refluxed for 20 hr under Nj. The mixture was acidified with dil H2S04, the H20 layer was separated, basified with 10% NaOH, extracted with CHC13, dried, and evaporated.The residue was chromatographed on A1203 and eluted with CeHe-EtaO (9:1). The eluate was converted into the picrate and recrystallized from EtOH-Me2CO to give IV • picrate (0.06 g, 11%),"mp 220-230°d ec, ir, 1723 cm'1. Anal. (C^H^NAc) C, , N. The free base was crystallized from Et20, mp 98-99°, identical with an authentic specimen, (mp, nmr, and tic).activity. Thanks are also due to Mr.