In the recent few years, especially since the introduction of phosphodiesterase-5 inhibitor, sildenafil, most researchers have focused their researches on biochemistry and physiology of erectile function. New progress has been made made in basic and clinic researches on pharmacotherapy for ED. In this article, the putative molecular or cellular mechanism of actions of the available centrally and peripherally acting drugs are reviewed, providing details about the current and most explosive area of drug research and development in erectile dysfunction.
Animals ; Apomorphine ; pharmacology ; therapeutic use ; Erectile Dysfunction ; drug therapy ; Humans ; Male ; Phosphodiesterase Inhibitors ; pharmacology ; therapeutic use ; Piperazines ; pharmacology ; therapeutic use ; Purines ; pharmacology ; therapeutic use ; Rats ; Sildenafil Citrate ; Sulfones ; pharmacology ; therapeutic use ; Yohimbine ; pharmacology ; therapeutic use

Viagra has become the first line drug for the treatment of erectile dysfunction since it was first introduced in 1998. Its efficacy and safety have been sidely acclaimed as being definite. This article presents a brief review about the advances in the studies of Viagra, including its therapeutic effect and safety, its protection of penile health, and its promotion of self-esteem and sexual relationship.
Erectile Dysfunction ; drug therapy ; Humans ; Male ; Penile Erection ; drug effects ; Personal Satisfaction ; Phosphodiesterase Inhibitors ; pharmacology ; therapeutic use ; Piperazines ; pharmacology ; therapeutic use ; Purines ; pharmacology ; therapeutic use ; Sildenafil Citrate ; Sulfones ; pharmacology ; therapeutic use

Antineoplastic Agents ; pharmacology ; therapeutic use ; Benzamides ; Clinical Trials, Phase II as Topic ; Drug Resistance, Neoplasm ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; pharmacology ; therapeutic use ; Pyrimidines ; pharmacology ; therapeutic use

OBJECTIVETo review and assess the update studies regarding selective serotonin reuptake inhibitors (SSRIs) in the treatment of premature ejaculation (PE) and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE.

DATA SOURCESUsing the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed.

STUDY SELECTIONPE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected.

RESULTSMany kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors (PDE(5)-Is) are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C (5-HT(2C)) receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression.

CONCLUSIONThe efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.

Clinical Trials as Topic ; Ejaculation ; drug effects ; Humans ; Male ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Serotonin Uptake Inhibitors ; adverse effects ; pharmacology ; therapeutic use ; Sexual Dysfunction, Physiological ; drug therapy ; Sildenafil Citrate ; Sulfones ; therapeutic use

Nitric oxide (NO) as a messenger and/or effector plays important roles in vivo. The decreased availability of NO or dysfunction in NO signaling has often been implicated in the development and progression of diseases, and design and research of NO-donating drugs has become one of the important strategies in drug discovery. In connection with authors' scientific practice, this article reviews the recent advances in the research of NO-donating drugs.
Animals ; Anti-Inflammatory Agents, Non-Steroidal ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Aspirin ; analogs & derivatives ; pharmacology ; therapeutic use ; Azo Compounds ; pharmacology ; Cardiovascular Diseases ; drug therapy ; Cell Line, Tumor ; Drug Design ; Humans ; Neoplasms ; drug therapy ; pathology ; Nitrates ; pharmacology ; therapeutic use ; Nitric Oxide ; metabolism ; Nitric Oxide Donors ; pharmacology ; therapeutic use ; Piperazines ; pharmacology ; Signal Transduction ; drug effects

Due to the complicated pathogenesis of cardiac arrhythmia, the safe and effective therapeutic strategies for cardiac arrhythmia remain an urgent medical problems in the recent years. In this paper, we introduced the research practice of anti-arrhythmic agents targeting on potassium ion channel. The research progress of anti-arrhythmic agents in up-to-date literatures were also reviewed and prospected.
Amiodarone ; analogs & derivatives ; chemistry ; pharmacology ; therapeutic use ; Animals ; Anti-Arrhythmia Agents ; chemistry ; pharmacology ; therapeutic use ; Arrhythmias, Cardiac ; drug therapy ; physiopathology ; Humans ; Hydantoins ; Imidazolidines ; chemistry ; pharmacology ; therapeutic use ; Molecular Structure ; Piperazines ; chemistry ; pharmacology ; therapeutic use ; Potassium Channel Blockers ; pharmacology ; therapeutic use ; Potassium Channels ; drug effects

OBJECTIVETo investigate the effect of Bushengzhuyang Fang (Yangjing Capsule, YJC) on penile erectile function and its action mechanisms in rats.

METHODSFifty-six male SD rats were randomly divided into seven groups of equal number: blank control, daidzein, daidzein + testosterone, daidzein + sildenafil, daidzein + low-dose YJC, daidzein + medium-dose YJC, and daidzein + high-dose YJC. The rats in the blank control group were treated intragastrically with normal saline and those in the other groups with daidzein at the dose of 100 mg per kg per day for 30 days. Then the last five groups received additionally testosterone (4 mg per kg per day), sildenafil (2.5 mg per kg per day), low-dose YJC, (0.315 mg per kg per day), medium-dose YJC (0.63 mg per kg per day), and high-dose YJC (1. 26 mg per kg per day), respectively. At 0, 30 and 60 days of treatment, we observed the apomorphine-induced spontaneous erectile response and pathological changes in the corpus cavernosum of the rats, recorded the number of penile erection and erectile incubation period, and determined the serum levels of testosterone (T) and luteinizing hormone (LH).

RESULTSAt 30 days of treatment, the number of apomorphine-induced erections was decreased, the erectile incubation period prolonged, and the serum levels of T and LH reduced remarkably in all groups of rats (P < 0.05). Compared with the findings at 30 days, the number of penile erections was significantly decreased at 60 days in the daidzein group (1.39 ± 0.42 vs 2.67 ± 0.33, P < 0.05) and daidzein + low-dose YJC group (1.33 ± 0.49 vs 2.83 ± 0.61, P < 0.05); the erectile incubation period was markedly ex- tended ([16.33 ± 3.11] vs [8.50 ± 0.93] min and [15.50 ± 3.21] vs [8.63 ± 1.54] min, P < 0.05); and the serum levels of T ([5.34 ± 0.89] vs [1.24 ± 0.30] ng/ml and [5.28 ± 1.12] vs [2.07 ± 0.76] ng/ml, P < 0.05) and LH ([3.62 ± 0.37] vs [2.09 ± 0.12] ng/ml and [3.79 ± 0.28] vs [2.17 ± 0.33] ng/ml, P < 0.05) were significantly reduced in the daidzein and daidzein + low-dose YJC groups, respectively. Pathological examination revealed slightly decreased cavernous sinuses and blood vessels in the corpus cavernosum of the rats in the daidzein + testosterone, daidzein + sildenafil, daidzein + medium-dose YJC, and daidzein + high-dose YJC groups as compared with those in the blank control group.

CONCLUSIONHigh-dose Yangjing Capsule is efficacious for the recovery of erectile function in rats, especially for phytoestrogen-induced erectile dysfunction.

Animals ; Apomorphine ; pharmacology ; Drugs, Chinese Herbal ; therapeutic use ; Erectile Dysfunction ; chemically induced ; drug therapy ; Humans ; Isoflavones ; pharmacology ; Luteinizing Hormone ; Male ; Penile Erection ; drug effects ; physiology ; Penis ; drug effects ; pathology ; Phytoestrogens ; Phytotherapy ; Piperazines ; therapeutic use ; Purines ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sildenafil Citrate ; Sulfonamides ; therapeutic use ; Testosterone ; therapeutic use ; Vasodilator Agents ; therapeutic use

Sildenafil increases the cyclic guanosine monophosphate (cGMP) by inhibition of a phosphodiesterase 5, thereby leading to an antinociceptive effect. The increased cGMP may exert the effect on an L-type calcium channel through the activation of protein kinase G (PKG). The purpose of this study was to examine the possible involvement of a PKG-L-type calcium channel on the effect of sildenafil at the spinal level. Catheters were inserted into the intrathecal space of male SD rats. Pain was induced by applying 50 microliter of a 5% formalin solution to the hindpaw. The sildenafil-induced effect was examined after an intrathecal pretreatment of a PKG inhibitor (KT 5823), or a L-type calcium channel activator (FPL 64176). Intrathecal sildenafil produced an antinociceptive effect during phase 1 (0~10 min interval) and phase 2 (10~60 min interval) in the formalin test. Intrathecal KT 5823 and FPL 64176 attenuated the antinociceptive effect of sildenafil during both phases. Sildenafil is effective against both acute pain and the facilitated pain state at the spinal level. In addition, the inhibition of an L-type calcium channel by activation of the PKG may contribute to the antinocieptive mechanism of sildenafil in the spinal cord.
Animals ; Calcium Channel Agonists/pharmacology ; Calcium Channels, L-Type/*physiology ; Carbazoles/pharmacology ; Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors/*physiology ; Dose-Response Relationship, Drug ; Male ; Pain/drug therapy/*physiopathology ; Pain Measurement ; Piperazines/*pharmacology/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Purines/pharmacology/therapeutic use ; Pyrroles/pharmacology ; Rats ; Rats, Sprague-Dawley ; Sulfones/*pharmacology/therapeutic use

Adult ; Antibiotics, Antineoplastic ; therapeutic use ; Benzamides ; Blast Crisis ; drug therapy ; Drug Resistance, Neoplasm ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Male ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; Sirolimus ; therapeutic use

Philadelphia (Ph) chromosome at (9; 22) reciprocal chromosomal translocation producing BCR-ABL fusion gene, emerges in almost all patients with chronic myeloid leukemia (CML). The protein product of BCR-ABL is a constitutively active tyrosine kinase that drives the abnormal proliferation of CML cells. Blast crisis (BC) is the terminal phase of CML, which is often associated with additional chromosomal and molecular secondary changes. Although the mechanisms responsible for transition of CML chronic phase (CP) into BC remain poorly understood, ample evidence suggests that it depends on synergy of BCR/ABL with other genes dysregulated during disease progression, and signaling pathways are abnormally activated by BCR/ABL. With the application of imatinib, a ABL-specific tyrosine kinase inhibitor, its remarkable therapeutic effects suggest that blast crisis transition will be postponed in most patients with CML. Rate of cumulative best response in CML-CP patients from the IRIS trial after 5 years are 98% for complete hematologic response, 92% for major cytogenetic response and 87% for complete cytogenetic response. However, a minority of CML-CP patients and most patients in progression either fail or respond suboptimally to imatinib. There are many distinct patterns of resistance, and ABL kinase mutations is a common finding associated with clinical resistance. Dasatinib and nilotinib can restore hematologic and cytogenetic remission in the majority of patients with primary failure or acquired resistance in chronic phase. This review illustrates the molecular mechanisms underlying transition to CML-BC, also addresses oneself to how and why imatinib resistance occurs.
Benzamides ; Blast Crisis ; drug therapy ; genetics ; Dasatinib ; Drug Resistance, Neoplasm ; drug effects ; Fusion Proteins, bcr-abl ; antagonists & inhibitors ; genetics ; Genes, abl ; drug effects ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; pathology ; Philadelphia Chromosome ; Piperazines ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; therapeutic use ; Pyrimidines ; pharmacology ; therapeutic use ; Thiazoles ; pharmacology ; therapeutic use ; Translocation, Genetic