Brian H. Vickery

Pharmaceutical compositions for the nasal delivery of compounds useful for the treatment of osteoporosis

A pharmaceutical composition for the nasal delivery of compounds useful for treating osteoporosis, comprising an effective amount of a physiologically active truncated analog of PTH or PTHrp, or salt thereof, in which amino acid residues (22-31) form an amphipathic α-helix, said residues (22-31) selected from (SEQ ID NOS: 85, 86, 26, 27, 28, 29, and 30); an absorption enhancer selected from the group consisting of dimethyl-β-cyclodextrin and the bile acid surfactants; and water is provided.

Reversible inhibition of testicular function by a gonadotropin hormone-releasing hormone antagonist in monkeys (Macaca fascicularis)

The potential of a gonadotropin-releasing hormone (GnRH) antagonist to inhibit reproductive functions in a male nonhuman primate (Macaca fascicularis) was evaluated. Continuous infusion of 2 mg/day of [N-Ac-D-Nal(2)1, D-pCl-Phe2, D-Trp3, D-hArg(Et2)6, D-Ala10]-GnRH (RS-68439) via osmotic minipumps for 9 weeks caused immediate and sustained reduction of serum luteinizing hormone and testosterone concentrations and led to azoospermia in three animals and to sperm counts less than 5 X 10(6) in a fourth. Testicular histology showed severe atrophy of Leydig cells and tubules. The endocrine parameters returned to normal within 2 weeks of termination of treatment. Seminiferous tubule function was restored 14 to 18 weeks after treatment, as indicated by normal ejaculate parameters. It is concluded that chronic GnRH antagonist treatment reversibly inhibits pituitary and testicular function in a nonhuman primate. GnRH antagonists may thus have a potential for clinical use in fertility control and in treatment of androgen-dependent tumors.

Assessment of a new spermicidal agent against ejaculated dog and human spermatozoa in vitro

The spermatostatic potencies of a new vaginal contraceptive agent, RS-37367, and a standard surfactant compound, nonoxynol-9, have been compared by using ejaculated dog and human spermatozoa. RS-37367 was 25 to 50 times more potent than nonoxynol-9 against dog spermatozoa. Nonparallel concentration-response lines were obtained against human spermatozoa. Concentrations of RS-37367 causing immediate spermatostasis against dog spermatozoa resulted in vesiculation of the plasma and outer acrosomal membranes of spermatozoa; similarly, immediately spermatostatic concentrations of nonoxynol-9 were associated with the previously documented generalized membrane stripping. The activities of both RS-37367 and nonoxynol-9 were affected by the concentration of dog spermatozoa in semen-compound mixtures. Short-term (5-minute) exposure of spermatozoa to concentrations of RS-37367 not immediately spermatostatic resulted in progressive immobilization of spermatozoa. Extensive washing of the spermatozoa was not able to reverse this effect, in contrast to spermatozoa transiently exposed to nonoxynol-9.