OBJECTIVE: To investigate the inhibitory effects of novel phosphodiesterase 4 inhibitor ZL-n-91 to the proliferation of leukemia cells L1210 and K562. METHODS: CCK-8 method was used to detect the effect of ZL-n-91 to the proliferation of L1210 and K562 cells, and the proliferation rate, IC RESULTS: ZL-n-91 showed a significant inhibitory effect to the proliferation of leukemia cells L1210 and K562 in a dose-dependent manner (P<0.001). After treated by ZL-n-91, the leukemia cells L1210 and K562 in the S-phase in cell cycle decreased significantly compared with those in control group (P<0.01). The apoptosis of leukemia cells L1210 and K562 could be induced by ZL-n-91 (P<0.001), and the expression level of apoptosis related protein BAX significantly increased. In the animal experiment, the result showed that ZL-n-91 could significantly inhibit the growth of subcutaneously transplantation tumor (P<0.05). CONCLUSION The novel phosphodiesterase 4 inhibitor ZL-n-91 can effectively inhibit the proliferation of leukemia cells L1210 and K562, which has the potential of anti-leukemia drug development.
Animals ; Cell Proliferation ; Humans ; K562 Cells ; Leukemia ; Mice ; Mice, Nude ; Phosphodiesterase 4 Inhibitors/pharmacology*

OBJECTIVETo compare the bronchofilating and antiallergic effects with piclamilast with ciclamilast, the second-generation phosphodiesterase 4 (PDE4) selective inhibitors.

METHODSEffects of piclamilast and ciclamilast on airway smooth muscle (ASM) at resting tension, carbachol-induced contraction and the synergistic effect of two agents on isoproterenol-induced bronchorelaxation were evaluated in the isolated tracheal strips of guinea pig in a cumulative manner in vitro. Slow reaction substance of anaphylaxis (SRS-A) release from lung tissues of the sensitized guinea pigs after antigen challenge was examined by bioassay. Antiallergic effect of piclamilast, ciclamilast and rolipram on the isolated ASM of sensitized guinea pigs were evaluated with Schultz-Dale reaction.

RESULTSPiclamilast and ciclamilast showed bronchorelaxant effect in ASM at resting tension. EC50 values of piclamilast and ciclamilast were 1.00 x 10(-5) mol/L and 0.84 x 10(-5) mol/L. Piclamilast and ciclamilast could both enhance the bronchodilating effect of isoproterenol in the isolated ASM of guinea pig, reduce the amount of SRS-A released from lung tissues of the sensitized guinea pigs and also inhibit ovalbumin (OA)-induced bronchoconstruction (Schultz-Dale reaction).

CONCLUSIONThe results indicate the bronchodilating effect of ciclamilast is as potent as piclamilast, but the antiallergic effect of ciclamilast is significantly more potent than that of piclamilast.

Animals ; Anti-Allergic Agents ; pharmacology ; Benzamides ; pharmacology ; Bronchodilator Agents ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Guinea Pigs ; In Vitro Techniques ; Isoproterenol ; pharmacology ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; Pyridines ; pharmacology

The remarkable therapeutic success of PDE5 inhibitors in the treatment of male erectile dysfunction has focused the attention of the researchers on better defining the properties of the individual inhibitors and PDE5 that contribute to the high affinity of these inhibitors for interaction with the PDE5 catalytic site. Recent molecular studies have demonstrated that vardenafil has high affinity for PDE5 and low dissociation rate from PDE5, which serves to explain why vardenafil works with low dosage, onsets quickly and has curative action in clinical practice. Moreover, the potency of vardenafil depends on its ring structure that resembles the purine moiety in cGMP.
Drug Interactions ; Erectile Dysfunction ; drug therapy ; Humans ; Imidazoles ; chemistry ; pharmacology ; Male ; Molecular Structure ; Phosphodiesterase Inhibitors ; chemistry ; pharmacology ; Piperazines ; chemistry ; pharmacology ; Sulfones ; chemistry ; pharmacology ; Triazines ; chemistry ; pharmacology ; Vardenafil Dihydrochloride

DA-8159, a selective inhibitor of phosphodiesterase type 5, was developed as a new drug for erectile dysfunction. The effect of DA-8159 on the electroretinogram (ERG) and the retinal histopathology were evaluated in rabbits. The ERG was performed prior to, and 1 and 5 hr after DA-8159 (5 to 30 mg/kg) administration. The plasma concentration of DA-8159 was determined at each time point, and retinal microscopic examination was also performed. There was no statistically significant ERG change at any dose or at any time. Though the 30 Hz flicker showed a prolongation of the implicit time at 5 hr after the administration of either DA-8159 15 mg or 30 mg/kg (p<0.05), but concurrent amplitude decreases were not statistically significant. At a dose of 5 mg/kg, no test drug was detected in the blood after either 1 or 5 hr. At either 15 mg/kg or 30 mg/kg, there was a dose-dependent increase in the blood concentration after 1 hr of drug administration, which decreased with time. In light and electron microscopic examinations of the retina, there was no remarkable change at any dose. These results suggest DA-8159 has a low risk potential to the retina, but further evaluation on the visual functions in human is needed.
3',5'-Cyclic-GMP Phosphodiesterase/*antagonists & inhibitors ; Animals ; Dose-Response Relationship, Drug ; Electroretinography/*drug effects ; Humans ; Male ; Phosphodiesterase Inhibitors/blood/*pharmacology ; Pyrimidines/blood/*pharmacology ; Rabbits ; Retina/*cytology/*drug effects

OBJECTIVETo evaluate the efficacy of sildenafil on nocturnal penile tumescence (NPT).

METHODSThirty-five patients with erectile dysfunction (ED), 28 cases of organic ED and 7 cases of psychogenic ED, were treated with sildenafil 100 mg before bedtime. The NPT of the patients was observed by using NEVA.

RESULTSErectile function significantly improved in the 28 cases of organic ED (P < 0.05), but not in the 7 cases of psychogenic ED (P > 0.05).

CONCLUSIONSildenafil can improve NPT of organic ED patients without sexual stimulation.

Adult ; Erectile Dysfunction ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Penile Erection ; drug effects ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; pharmacology ; Sildenafil Citrate ; Sulfones ; pharmacology

OBJECTIVE: Scandix pecten-veneris L. is a less studied wild edible herb and is considered an extinct plant species in many parts of the world. This study was designed to evaluate its phytochemical composition and biological potential of S. pecten-veneris L. METHODS: Phytochemicals including alkaloids, flavonoids, polyphenols, and tannins were determined in extracts of S. pecten-veneris. Antioxidant activity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), while reducing power was tested by ferric reducing/antioxidant power (FRAP) assay. Antimicrobial activity against seven bacterial and four fungal strains was evaluated using agar well diffusion assay. Enzymes inhibition study was performed for urease, phosphodiesterase-I, and catalase-II. RESULTS: S. pecten-veneris showed moderate antiradical activity and reducing potential of hydroxyl radicals to about 20% of the initial value. The antioxidant activity of various extracts of S. pecten-veneris showed a linear correlation with total phenolic contents in the order of water>n-butanol>chloroform>ethyl acetate>methanol extracts. S. pecten-veneris leaves showed the highest inhibitory activity against Staphylococcus aureus while the highest antifungal activity was observed against Candida albicans. The plant extract was most potent against urease enzymes but showed moderate activity against phosphodiestrase-I and carbonic anhydrase-II. CONCLUSIONS Our data demonstrate that in addition to its culinary uses, S. pecten-veneris has good medicinal potential and hence could be used for treating some specific health ailments.
Animals ; Anti-Infective Agents/pharmacology* ; Antioxidants/pharmacology* ; Apiaceae/chemistry* ; Enzyme Inhibitors/pharmacology* ; Phosphodiesterase Inhibitors/pharmacology* ; Phytochemicals/analysis* ; Plant Extracts/pharmacology* ; Plants, Edible/chemistry* ; Staphylococcus aureus/drug effects* ; Urease/antagonists & inhibitors*

No abstract available.
Animals ; Anoxia/*drug therapy ; Diabetes Mellitus, Experimental/*complications ; Diabetic Nephropathies/*drug therapy ; Kidney Tubules/*drug effects ; Male ; Pentoxifylline/*pharmacology ; Phosphodiesterase Inhibitors/*pharmacology

AIMTo examine the changes in the erectile function in diet-induced obese rats and investigate the oral efficacy of DA-8159, a new phosphodiesterase type 5 (PDE5) inhibitor, on penile erection in obese rats.

METHODSThe rats were fed a high-energy diet for 12 weeks and divided into three groups: an obesity-resistant (OR) control group, an obesity-prone (OP) control group, and an OP-DA-8159 treatment (DA-8159) group. The electrostimulation-induced erectile responses were measured in all groups. The body weight, plasma cholesterol, triglyceride and glucose levels were also measured.

RESULTSIn the OP control group, the maximum intracavernous pressure (ICP) and ICP/blood pressure (ICP/BP) ratio after electric stimulation were significantly lower than those in OR control group. The corresponding area under the curve (AUC) of the ICP/BP ratio, the detumescence time and the baseline cavernous pressure were also lower than those in the OR control group, but this difference was not significant. The body weight gain, plasma cholesterol and triglyceride level in the OP group were significantly higher than those in the OR group. After administering the DA-8159, a significant increase in the maximum ICP and the ICP/BP ratio were observed. The corresponding AUCs in the DA-8159 group were also higher than those in the two control groups. Furthermore, the detumescence time was significantly prolonged after treatment with DA-8159.

CONCLUSIONThese results demonstrate that diet-induced obesity affects the erectile function in rats and these erectile dysfunction (ED) can be improved by the treatment with DA-8159, indicating DA-8159 might be a treatment option for ED associated with obesity.

Animal Feed ; Animals ; Diet ; Erectile Dysfunction ; etiology ; prevention & control ; Male ; Obesity ; etiology ; physiopathology ; Penile Erection ; drug effects ; physiology ; Phosphodiesterase Inhibitors ; pharmacology ; Pyrimidines ; pharmacology ; Rats ; Sulfonamides

The enzyme phosphodiesterase-5 (PDE-5), widely distributed in the heart, smooth muscle, and blood vessels, catalyzes the hydrolysis of cyclic guanosine monophosphate (cGMP), a potent vasodilator, and is also a nitric oxide (NO) donor. Tadalafil is the first PDE 5 inhibitor approved by FDA for the treatment of ED. Recent studies have shown several pleiotropic beneficial effects of PDE-5 inhibitors in patients with cardiovascular diseases (coronary heart disease, hypertension, heart failure, and pulmonary arterial hypertension) and diabetes mellitus. It has been demonstrated that tadalafil can not only improve sexual function, but also elevate the endothelial cell-derived NO level, activate protein kinase A, upregulate the intracellular Ca2+ concentration, and improve hemodynamic indexes. Thus, the PDE-5 inhibitor tadalafil, with its cardiovascular-protective effect, can be a therapeutic option for the treatment of ED patients with cardiovascular disease.
Carbolines ; pharmacology ; therapeutic use ; Cardiovascular Diseases ; complications ; drug therapy ; Erectile Dysfunction ; complications ; drug therapy ; Humans ; Male ; Phosphodiesterase 5 Inhibitors ; pharmacology ; therapeutic use ; Tadalafil

OBJECTIVETo obtain related pharmacodynamic data for the clinical experiment by observing the sexual activities of male rats after using sildenafil ciltrate through stomach irrigation.

METHODSForty male Sprague-Dawley rats were distributed into 4 groups with different dosages (control with distilled water, low dosage: 0.08%, medium dosage: 0.24% and high dosage: 0.72%). After the male Sprague-Dawlay rats were mated with their female counterparts in pairs, the latent period of chasing, the frequencies of chasing in 60 minutes, the latent period of intercourse and the frequencies of intercourse in 60 minutes were recorded.

RESULTSCompared with the control, the frequencies of chasing were significantly increased and the latent periods of chasing were significantly shortened in both high dosage and medium dosage groups after using sildenafil (P < 0.01); The frequencies of intercourse in 60 minutes were significantly increased and the latent periods of intercourse were significantly shortened in all the groups after the use of sildenafil.

CONCLUSIONSThe sexual activities of male rats treated with sildenafil were significantly activated.

Animals ; Dose-Response Relationship, Drug ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; Piperazines ; pharmacology ; Purines ; Rats ; Rats, Sprague-Dawley ; Sexual Behavior, Animal ; drug effects ; Sildenafil Citrate ; Sulfones