Suppressing aggressive behavior with analogs of allopregnanolone (epalon).

3alpha-Hydroxy-20-oxo-5alpha-pregnan-21-yl hemisuccinate (8) was produced by partial acylation of 3alpha,21-dihydroxy-5alpha-pregnan-20-one (14). 3alpha-Fluoro-5alpha-pregnan-20-one (9) was prepared by treatment of 3beta-hydroxy-5alpha-pregnan-20-one (11) with DAST and by solvolysis of tosylate 12 with tetrabutylammonium fluoride. A behavioral test on mice was performed using 3alpha-hydroxy-5alpha-pregnan-20-one (1) and compounds 8 and 9. Compound 8 was found to be inactive, while the fluoro derivative 9 selectively reduced aggressive behavior in mice more than the corresponding 3alpha-hydroxy compound 1; locomotion and other behavioral features were not affected.

[The effect of phytogenic brassinosteroid steroidal hormones on transport of 86Rb+ ions into human erythrocytes]. / Rostlinné steroidní hormony brassinosteroidy a jejich úcinek na transport iontu 86Rb+ do lidských erytrocytu.

The uptake of 86Rb+ ions by human erythrocytes as the measure of inhibition or stimulation of Na+, K(+)-ATPase by synthetic brassinolides, steroid fytohormonal promotors, was determined. No compound of the 12 tested brassinosteroids exerted higher inhibition of ATPase than digitoxin. A lower but significant inhibition of ion transport by 3 of tested derivatives, and a stimulation by 4 compounds was found. All active compounds were steroids with a 7-membered B-ring with an oxygen atom in the position 7a and with an oxogroup in position 6, i.e. they contained an lactone ring which is characteristic for natural brassinosteroids.

[Therapeutic use of synthetic Gn-RH-Dirigestran in disorders of the reproductive cycle in cows from low-fertility herds]. / Terapeutické pouzití syntetického Gn-RH-Dirigestranu pri poruchách reprodukcního cyklu krav v chovech s nízkou plodností.

Synthetic Gn-RH-Dirigestran Spofa was used for the treatment of 121 cows with functional ovarial disorders. Out of this total number, 41 cows showed no postpartal and no post-service symptoms of oestrus, 59 returned to oestrus with irregular cycles, and 21 cows showed an irregular course of oestrus. The treatment was made in herds with a low conception rate (32-37% conceptions after the first insemination, service period 108 to 142 days). On the whole, 80.1% of the treated cows got in calf, 53.7% conceived after the first insemination. The average time from treatment to successful insemination was 39 days. The treatment was started 148 days from parturition, on an average. The average insemination index of the treated cows was 1.44. As to cows out of heat, 70.7% got in calf on the whole and 51.2% after the first insemination, the therapeutic service period (TSP) being 44 days. Out of the cows returning to oestrus with an irregular cycle, 84.7% got in calf and 52.5% got in calf after the first insemination with the TSP of 37 days, and the cows with irregular cycle the conception was recorded in 85.7% (61.9% after the first insemination with the average TSP of 35 days). On the whole, 82% of treated cows showed clearly visible symptoms of oestrus after the application of Dirigestran. The pregnancy of the whole set (121 treated cows) was higher by 15 to 21% after the first insemination and by 41 to 49% after all inseminations, as compared with the pregnancy of normally inseminated cows in these herds. The results show that the treatment of the functional disorders of ovaries is also practicable in cows in herds with a decreased fertility if this treatment is not impaired by spermiotoxicity or embryotoxicity owing to the effects of inadequate secretions of sexual organs caused by incorrect nutrition or infections.

D-homoandrostanes. 4. The incubation of some D-homo-5 alpha-androstanes with Rhizopus nigricans.

Nine dioxygenated D-homoandrostanes were incubated with Rhizopus nigricans to investigate the effect of D-ring modification on microbiological hydroxylation. Structure determination of the products by NMR spectroscopy, and in certain cases independent synthesis of their oxidised products, showed that in contrast to 5 alpha-androstanes the majority of the compounds were hydroxylated in the "reverse" mode, and only D-homo-5 alpha-androstane-3,17-dione was hydroxylated in the "normal" mode to any extent. Stereospecific ring D-hydroxylation at C(17 alpha) was observed for both D-homo-5 alpha-androstane-3,6- and 3,7-diones.

Androgen receptor binding and antiandrogenic activity of some 4,5-secoandrostanes and ring B cyclopropanoandrostanes.

Eight androstane derivatives with modified ring A or B (4,5-secoandrostanes and ring B cyclopropanoandrostanes) were assayed in vivo on mice for their antiandrogenic activity and the effect was compared with that of cyproterone acetate. The inhibition of dihydrotestosterone binding to rat prostate cytosol and to human plasmatic sex hormone binding protein was correlated with the in vivo effect. The antiandrogenic activity of 6 alpha,7 alpha-cyclopropano-5 alpha-androstane-3 beta,17 beta-diol was nearly as high as that of cyproterone acetate. The opening of ring A of androgens, such as testosterone or 17 alpha-methyltestosterone, moderately reduced the binding and changed the biological activity to weakly antiandrogenic.

Bromocriptine in parkinsonism. A long-term study.

Bromocriptine was given in a controlled trial to 86 parkinsonian patients. Eight of 30 previously untreated patients with early and mild disease showed sustained benefit for two years and did not develop "on-off" effects or dyskinesias. Only two of 23 patients unable to tolerate or failing to respond to levodopa benefited from bromocriptine. Thirty-three patients with residual disabilities despite maximum tolerated doses of levodopa were also given bromocriptine: although benefit accrued, treatment was abandoned because of unacceptable side effects, and there was no improvement in the 11 with severe "on-off" disabilities. Although it was found that benefit from 70 mg daily of bromocriptine was comparable to that from 750 mg of levodopa with carbidopa, bromocriptine seems to offer no advantage to the majority of patients who have received or are receiving levodopa and/or carbidopa.

Deprenyl in Parkinson's disease.

In a double-blind crossover trial, (-)-deprenyl, a fast-acting selective monoamine-oxidase-B inhibitor without a "cheese effect", was given to 41 patients with idiopathic Parkinson's disease who were receiving maximum tolerated doses of levodopa either alone or combined with carbidopa ("Sinemet"). In a dose of 10 mg, daily or on alternate days, (-)-deprenyl prolonged the therapeutic effect of levodopa and was effective in mild "on-off" disabilities with end-of-dose akinesia; the majority of patients with nocturnal and early-morning akinesia also improved. No statistically significant improvement occurred in diurnal akinesia, and there was no improvement in patients with severe on-off disabilities with freezing and rapid oscillations ("yo-yo" effect). Levodopa-induced dyskinesias were aggravated in 14 patients. In 5 previously untreated patients, (-)-deprenyl alone gave no benefit, but when it was used with levodopa and carbidopa a mean dosage reduction of 200 mg levodopa daily was possible. Depression, present in 15 patients, was unchanged. (-)-Deprenyl in combination with smaller total daily doses of levodopa and a peripheral decarboxylase inhibitor may prove useful in reducing the frequency and severity of some types of on-off effect with overall benefit comparable to that obtained with larger doses of levodopa.