Abstract |
We have reported that denbufylline, a phosphodiesterase 4 ( PDE4) inhibitor, inhibits bone loss in Walker256/S tumor-bearing rats, suggesting therapeutic potentiality of a PDE4 inhibitor in osteopenia. In the present study, effects of a new PDE4 inhibitor, 1-n-butyl-3-n-propylxanthine (XT-44), in bone were evaluated in cell cultures and animal experiments. In rat bone marrow culture, XT-44 stimulated mineralized-nodule formation, whereas it inhibited osteoclast-like cell formation in mouse bone marrow culture. In Walker256/S-bearing rats (6-week-old female Wistar Imamichi rats), rapid decrease in bone mineral density (BMD) was prominent, and oral administration of XT-44 (0.3 mg/kg, every 2 days) inhibited the decrease in BMD. In the second animal experiment, female Wistar rats (6-week-old) were sciatic neurectomized, and XT-44 was orally administered to these rats every 2 days for 4 weeks. XT-44 administration (0.3 mg/kg) recovered BMD in these neurectomized animals. Furthermore, 19-week-old, female Wistar rats were ovariectomized (OVX), and 15 weeks after surgery, these rats were orally administered XT-44 every 2 days for 8 weeks. XT-44 treatment (1 mg/kg) increased the BMD of OVX rats. These results indicate that XT-44 could be a candidate as a therapeutic drug for treating osteopenia including osteoporosis.
|
Authors | Y Waki, T Horita, K Miyamoto, K Ohya, S Kasugai |
Journal | Japanese journal of pharmacology
(Jpn J Pharmacol)
Vol. 79
Issue 4
Pg. 477-83
(Apr 1999)
ISSN: 0021-5198 [Print] Japan |
PMID | 10361888
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- 1-n-butyl-3-n-propylxanthine
- Phosphodiesterase Inhibitors
- Purinones
- Pyrrolidinones
- Xanthines
- 3',5'-Cyclic-AMP Phosphodiesterases
- Cyclic Nucleotide Phosphodiesterases, Type 4
- zaprinast
- Rolipram
- 1-Methyl-3-isobutylxanthine
|
Topics |
- 1-Methyl-3-isobutylxanthine
(pharmacology)
- 3',5'-Cyclic-AMP Phosphodiesterases
(antagonists & inhibitors)
- Animals
- Body Weight
(drug effects)
- Bone Density
(drug effects)
- Bone Diseases, Metabolic
(drug therapy)
- Bone Marrow Cells
(cytology, drug effects)
- Cyclic Nucleotide Phosphodiesterases, Type 4
- Denervation
- Dose-Response Relationship, Drug
- Female
- Femur
(metabolism)
- Giant Cells
(cytology, drug effects)
- Male
- Mice
- Osteoblasts
(cytology, drug effects)
- Osteoclasts
(cytology, drug effects)
- Osteogenesis
(drug effects)
- Ovariectomy
- Phosphodiesterase Inhibitors
(pharmacology)
- Purinones
(pharmacology)
- Pyrrolidinones
(pharmacology)
- Rats
- Rats, Wistar
- Rolipram
- Sciatic Nerve
(surgery)
- Xanthines
(pharmacology)
|