Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline-induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline-induced cardiovascular toxicity.

The aerobic metabolism in biological systems, produces reactive oxygen species (ROS) known as prooxidants even in basal conditions. If the formation of prooxidants increases, it leads to oxidative stress/damage. Various diseases in humans (cancer, chronic diseases, cardiovascular problems etc.) accompanies with prooxidant damage. Endogenous and exogenous antioxidants protect biomolecules against the damage of prooxidants. Flavonoids are potent antioxidant molecules, which scavenge free radicals in vitro. They are found in fruits, vegetables, bark, roots, flowers and certain beverages. It has been reported that these natural products produce a wide variety of biological effects, like antiviral, anti-allergic, anti-inflammatory, anti-carcinogenic, antidiabetic effects. Flavonoids are important for human diet and have beneficial effects on health like chelating trace elements involved in free radical production, scavenging ROS and upregulating or protecting antioxidant defenses. In addition, they have known to modulate different cytochrome P450 enzymes such as CYP1A1/1A2, CYP1B1, CYP2C9, and CYP3A4/3A5. Flavonoids and their metabolites in organism may cause flavonoid-drug interaction, and it may lead to toxicity of drug or inefficient therapeutic effects of drug. However, knowledge on the mechanisms of action of flavonoids is still not fully understood. The information about correlation of structurebiological effect is limited. There are six major subclasses of flavonoids are flavanols, flavanones, flavonols, flavones, anthocyanidins, and isoflavones. This review summarizes the types of flavonoids, possible mechanisms of action and pharmacokinetic specialties, bioavailability, properties and drug interactions of these flavonoids.

The influence of serotonin (5-hydroxytryptamine, 5-HT) on human ureteral smooth muscle was explored in a series of in vitro experiments. 5-HT evoked a dose-dependent contraction of the ureter. The effect of 5-HT was unaltered by blockade of 5HT₃ and 5HT₄ receptors and muscarinic cholinergic receptors. The 5HT₂ receptor antagonist ketanserin (KT; 10^––5–10^––4M) and mixed 5HT₁/5HT₂ receptor antagonist methysergide (MS; 5 × 10^––5M) inhibited the effect of 5-HT. Since the antagonist dissociation constant at 5HT₂ receptors for both KT and MS is found to be approximately 10^––9M, it is concluded that this contractile effect may have been mediated by some other, as yet uncharac-terized 5-HT receptor. We believe that 5-HT is a potential neurotransmitter in the human upper ureteral smooth muscle.

The aim of this study is to evaluate the effects of hypercholesterolemia in thoracic aorta (TA), mesenteric artery (MA), renal artery (RA), and corpus cavernosum (CC) isolated from cholesterolfed rabbits. For determination of the maximum detrimental effect, vasorelaxation and vasoconstriction results of arteries and CC have been compared. Animals were fed with a diet that contained 2% w/w cholesterol and 2% w/w high cholesterol plus resveratrol (4 mg kg -1 per day) for 6-week duration. Total cholesterol levels in the plasma were measured. Vascular and endothelial functions in RA, TA, MA, and CC were assessed by isolated tissue bath with cumulative doses of acetylcholine and sodium nitroprusside. The statistical significance of differences of groups was analyzed by means of one-way ANOVA or Student's t-test. P-values o0.05 were considered significant. There have been no significant changes on plasma total cholesterol levels between cholesterol and cholesterol þ resveratrol-treated groups. Vasorelaxation responses to acetylcholine in resveratroltreated group showed significant changes when compared with hypercholesterolemic group. No statistically significant differences were seen between non-receptor-mediated vasorelaxation responses between the three groups. Resveratrol might be an effective treatment in the prevention of atherosclerotic changes in arteries and CC. The initial effects of hypercholesterolemia on erectile dysfunction and endothelial dysfunction may be precluded with resveratrol. This protective effect may also ensure the prevention of coronary arterial diseases and renovascular diseases in hypercholesterolemic patients.

Men seem to have a higher activity relative to women for the drug efflux transporter P-gp. Our results suggest that carvedilol will cause drug interaction with digoxin following the inhibition of P-gp-mediated transcellular transport of digoxin in males.