Guanadrel. A new antihypertensive drug.

Guanadrel sulfate, a new adrenergic neuron inhibitor similar to guanethidine sulfate, was tested on 199 outpatients by 11 investigators. The patients had mild, moderate, or severe hypertension as determined by diastolic blood pressures of 95 to 105, 106 to 114, and 115 to 120 mm Hg, respectively. Guanadrel was found to be an effective antihypertensive agent for all levels of hypertension. Since guanadrel has a short onset of action and a short offset of action, which prevents many of the side effects of guanathidine, the dosage could be adjusted rapidly and safely. At low doses side effects are infrequent. There was no organ toxicity and no CNS effect. Guanadrel should be an effective step II or step III drug for treatment of hypertension.

Reproduction in aging normal and neonatally androgenized female rats.

Decline in reproductive success was compared in normal and neonatally androgenized female rats permitted to receive 1 or 5 ejaculations during each of 7, 5, 3, or 1 mating test. Exposing the females to .5 microgram of testosterone propionate on Day 3 of life increased their age-related rate of decline in the number of successful pregnancies and offspring born in each litter as well as in behavioral receptivity. In both normal and neonatally androgenized animals, fertility and receptivity were greater in animals receiving five ejaculations rather than one ejaculation and in those having multiple pregnancies rather than a single or no prior pregnancy. Perinatally androgenized animals appear to provide a useful model for studying factors influencing age-dependent reproductive processes.

Modifications induced by neonatal steroids in reproductive organs and behavior of male rats.

Male rats injected on Day 3 neonatally with .01, .1, 1, 10, 100, or 1,000 micrograms of estradiol benzoate (EB), 10,000 microgram of testosterone propionate (TP), or sesame oil were subsequently examined for testicular, penile, and accessory organ development. Sexual behavior was evaluated during therapy with fluoxymesterone (FM) and then with TP. Estradiol benzoate in dosages greater than 1.0 micrograms delayed testicular descent, reduced the size and hormone responsiveness of reproductive organs, and decreased sexual behavior in a dose-dependent manner. The 10,000-microgram dosage of neonatal TP delayed testicular descent and reduced sexual behavior to levels near those of the 10--100 micrograms EB groups, but it produced no significant penile or accessory organ changes. Neither reduced peripheral organ development nor inhibited neonatal testicular secretions fully explain reductions in male behavior following large dosages of neonatal TP. Neonatal androgen may reduce the responsiveness of central nervous system neurons governing male sexual behavior after being converted to estrogen or by directly altering steroid receptor systems.

Evaluation of prenatal androgen and ovarian secretions on receptivity in female and male rats.

Offspring of rats infected daily from Day 16 through Day 20 of gestation with either 2 mg of testosterone propionate (TP) in .1 ml of sesame oil or oil alone were tested for sexual receptivity following injections of 3.3 microgram of estradiol benzoate (EB) and .5 mg of progesterone (P) beginning at 40, 80, or 120 days of age. At each age, neonatally gonadectomized males and females from TP-injected litters exhibited less receptivity than corresponding oil-injected controls. Prenatally androgenized females were similar to neonatally castrated oil-injected males at all ages. Ovarian implants from birth to 35 days of age significantly increased receptivity in neonatally castrated males and androgenized females. Increasing the age at which testing was initiated systematically reduced receptivity in all groups.