Abstract
The antiaccelerator activities of a series of nitrogen-containing steroid derivatives have been determined in the heart-lung preparation of the dog. Atropine was without influence upon this activity.
The most active compounds were the 16-piperidino derivatives of pregnenolone and allopregnane. Changes of nucleus from pregnenolone to allopregnanediol or to pregnanediol had no marked effect on activity. Esterification at C.3 was also innocuous. Conversion of the nitrogen to a tertiary or quaternary form was associated with a marked decrease in activity. On C.l6 a piperidine ring led to highest potency. Replacement by methylpiperidine, pyrrolidine, morpholine, cyclohexylamine, or diethylamino-propylamine led to decreased activity while a propylamine group there was as effective as the piperidine ring.
A representative compound showed a negative chronotropie action, a negative inotropic action, and a slight blockade of the peripheral vasocon-strictor effect of levarterenol.
When some of the compounds were given in conjunction with a sympathomimetic amine irregularities were observed. These consisted of irregular P-R intervals, A-V block or A-V disociation.
It was concluded that the antagonism between these compounds and the sympathomimetic amines on the heart rate is probably physiological in nature.
Footnotes
- Received August 14, 1959.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|