The Wonders of Phosphodiesterase‑5 Inhibitors: A Majestic History

The Nobel Prize winning discovery of nitric oxide (NO) in 1986 was the starting point for a new innovation in drug discovery. NO acting as a mediator at different physiological systems is believed to be involved in many physiological and pathological conditions through the formation of the second messenger cyclic guanosine monophosphate (cGMP). cGMP‑dependent vasodilation effect of NO is important in regulating pulmonary and systemic pressures, maintaining penis erection, preventing atherosclerosis, preventing platelet aggregation, and protecting and controlling cardiac functions. The main enzyme involved in the termination of cGMP effects is phosphodiesterase enzyme 5 (PDE‑5), which is overexpressed in ventricular hypertrophy and heart failure. A milestone in drug discovery was the selective inhibitors of PDE‑5 that developed to be a multibillion dollar blockbuster in drug market. PDE‑5 inhibitors are approved for the treatment of erectile dysfunctions (EDs), pulmonary hypertension, and benign prostatic hypertrophy. They are also under clinical trials for their cardiac protection against damage induced by ischemia or heart failure. This review article is an update about the pharmacotherapeutics of PDE‑5 inhibitors and the majestic history that led to their discovery. The information reported in this review was obtained from the electronic sources of different databases such as PubMed Central, Google Scholar, and Scopus. Keywords used for search included cGMP (mechanisms and functions), EDs (drugs used), nitric oxide, and PDE‑5 inhibitors (clinical applications). A total of 165 articles were studied, of which 45 articles were referred to in this review.Keywords: Cyclic guanosine monophosphate, Nitric oxide, Phosphodiesterase enzyme 5 inhibitor

The effect of GABAmimetics on the duration of immobility in the forced swim test in albino mice

Objectives: Studies regarding the role of gamma aminobutyric acid (GABA) in depression are conflicting. Therefore, it was decided to examine the effect of different drugs that enhance the GABA system on the time of immobility induced by the forced swim test (FST).Materials and methods: Adult albino mice were divided into several groups of six animals. Each group received an intraperitoneal injection of either imipramine (10, 20, or 30 mg/kg), diazepam (0.5, 1, or 2 mg/kg), vigabatrin (100, 200, or 300 mg/kg), zolpidem (2.5, 5, or 10 mg/kg), or alprazolam (1, 2.5, or 5 mg/kg). Control groups received the appropriate vehicle. One hour after injection, the duration of immobility was measured for 5 min in the FST. The percentage change in the duration of immobility from the control was calculated for each group. The statistical test of the difference between the treated and the control groups was calculated using unpaired Student’s t-test.Results: Imipramine produced a significant dose-dependent decrease in the duration of immobility (78, 74, and 56%, respectively). Different doses of diazepam, vigabatrin, and zolpidem produced a significant increase in the duration of immobility (119, 126, and 128%), (116, 124, and 128%), and (108, 109, and 119%), respectively. The two low doses of alprazolam produced a significant increase (115 and 120%), while the high dose produced a significant decrease in the duration of immobility (74%).Conclusion: Increasing central GABAergic activity by different mechanisms has resulted in a depressant-like activity measured as an increase in the duration of immobility in the FST model of depression.Keywords: GABAmimetics; forced swim test; diazepam; vigabatrin; zolpidem; alprazola

Cross-sectional pilot study about the health status of diabetic patients in city of Misurata, Libya

Background: Being a leading cause of death worldwide, epidemiological studies about diabetes mellitus have encouraged governments to initiate or improve local diabetes monitoring and prevention strategies. Objective: The main objective of this study was to examine the profile of diabetic patients in the city of Misurata, the third largest city in Libya. Methods: 260 diabetic cases of both gender randomly selected from the total number of patients admitted to the centre of diabetes and endocrine disorders, Misurata -Libya for the period between January to March 2008. Data collected from patients’ files and by directly questioning the patients. SPSS software version 13 was used for the statistical analysis and presentation of the data. Results: 87% of all patients were type 2 diabetics, while only 9.9% were type 1. 73% of all patients had family history of diabetes. 52% of all diabetic patients were obese, with more obesity in females (70% of females) than males (33.8% of males). Obesity was more pronounced in type 2 patients (56.8%) than in type 1 patients (11.5%). 38% of all patients were treated with insulin while 35.4% were treated with oral hypoglycemics. Meanwhile 32.6% of type 2 diabetic patients were treated with insulin. Only 9.2% of all patients had fasting blood sugar below 140 mg/dl, whereas 55% had levels in the range of 140-180 mg/dl, while 35.8% had levels above 180 mg/dl. Microvascular complications included retinopathy (16.2% of all patients), neuropathy (11.2%), nephropathy (1.5%) and combination of neuropathy and retinopathy (6.5%). Conclusion: High percentage of risk factors including obesity, family history of diabetes, hypertension and microvascular complications requires a Libyan national policy for the surveillance, prevention and control of diabetes and its complications