IRANIAN JOURNAL OF PHARMACOLOGY AND THERAPEUTICS (IJPT)
Year:2005 | Volume:4 | Issue:2|Papers Count:17

Determination of sildenafil by various methods and in various media is reviewed in this paper. The methods used consist of ultraviolet (UV) spectroscopy, thin layer chromatography (TLC), and high-performance liquid chromatography (HPLC). These methods were used to determine the amount of sildenafil in pharmaceutical preparations, soft drinks, and biological liquids. HPLC was used for evaluation of pharmacokinetic parameters of sildenafil. It is concluded that HPLC is the most reliable and applicable method in this regard. 

Clinically healthy adult black Bengal female goats were used to investigate the pharmacokinetics of closantel following intravenous administration (10 mg/kg) both in healthy and in liver damaged goats. Induction of liver damage was done by subcutaneous injection of carbontetrachloride at 0.75 mL/kg on three occasion at 48 h interval. After administration of drug, blood samples were collected in heparinized test tubes at pre- determined time. The drug concentration in plasma was measured by double beam UV– Vis  spectrophotometer at 222 nm. In vitro plasma protein binding of closantel was also carried out. Cmax (118.82 ± 4.85 μg/mL) and Cmin (4.69 ± 0.72 μg/mL) of closantel were recorded at 0.08 and 48 h respec-tively after i.v. administration to healthy goats, while the above values were 144.67 ± 2.50 and 3.93 ± 0.05 μg/mL at 0.08 and 48 h respectively in liver damaged goats. The t½β, ClB and Vdarea values were 12.92 ± 1.30 h, 0.008 ± 0.0005 L/kg/h and 0.15 ± 0.01 L/kg respectively in healthy goats, while these values were 12.84 ± 0.38 h, 0.008 ± 0.001 L/kg/h and 0.16 ± 0.005 L/kg respectively in liver damaged goats. Binding capacity and association rate constant of closantel were not altered significantly in liver damaged animal compared to healthy animal. Liver damaged condition did not alter significantly the pharmacokinetic parameters of closantel.

Methanolic leaf extracts of Eucalyptus camaldulensis were investigated for in vitro antifungal activities against Microsporum canis, Microsporum gypseum, Tricophyton rubrum, Tricophyton schoenleinii, Trico-phyton mentagrophytes and Epedermophyton floccosum. The studies were carried out using broth dilu-tion method, agar dilution method and inhibitory zone estimation. The effects of the plant extract were compared with those of griseofulvin. Eucalyptus camaldulensis showed antifungal activity against all the dermatophytes tested with MIC values ranging from 0.4 to 1.6 mg/mL using inhibitory zone estimation, 0.4-1.6 mg/mL using agar dilution method and 0.2 to 1.6 mg/mL using broth dilution method. The mini-mum fungicidal concentration (MFC) of the extracts ranged from 0.8 to 6.4 mg/mL. The results obtained suggest that E. Camaldulensis has anti-dermatophyte activity.  

Quercetin is a typical flavonoid with diverse biological effects, attributable to its free radical scavenging activity. Bioavailability of quercetin aglycone and its glycosides is an important factor for its antioxidant activity in vivo. A severe limitation exists and is imputable to very poor absorption of quercetin when ad-ministered orally. To overcome this limitation, development of a value added herbal formulation in combi-nation with phospholipids has been made which has better absorption and utilization profiles. Free radical scavenging activity of quercetin–phospholipid complex (equivalent to quercetin 10mg and 20 mg/kg body wt.) and free quercetin (10 mg and 20 mg/kg body wt.) was evaluated in oxidative stress condition in al-bino rats induced by carbon tetrachloride intoxication. The degree of protection of liver was estimated by evaluating status of enzymes like super oxide dismutase (SOD), catalase; lipid peroxidation profile in terms of thiobarbituric acid reactive substances (TBARS), reduced glutathione, glutathione peroxidase, glutathione reductase and glutathione–S–transferase. Quercetin–phospholipid complex restored the re-duced enzyme levels of liver glutathione system as well as impaired levels of other enzymes which are significant with respect to carbon tetrachloride treated group (p < 0.05 and < 0.01). For all enzymes tested, the complex at different dose levels produced better effects than free quercetin at same doses. Thus the results obtained ascertain the superiority of quercetin–phospholipid complex over free quercetin in terms of better free radical scavenging activity.  

The pharmacokinetic studies of enrofloxacin were investigated in yak (Bos grunniens L.) after administration of enrofloxacin by intramuscular route at 5 mg⋅kg-1 body weight. Blood samples were collected from the jugular vein at predetermined time intervals after drug administration. Plasma was separated and analyzed for enrofloxacin by reverse-phase high performance liquid chromatography. Various pharmacokinetic parameters were calculated using a non-compartmental model. The elimination half-life (t½), area under plasma concentration-time curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), apparent volume of distribution (Vd), total body clearance (ClB) and apparent first-order elimination rate constant (K) of enrofloxacin were 2.79±0.60 h, 5.35±1.29 mg h mL-1, 21.50±8.60 mg h2 mL-1, 4.02±0.87 h, 3.76±0.83 Lkg-1, 935.09 ± 236.45 ML h-1 kg-1 and 0.25±0.07 h-1, respectively after the administration of enrofloxacin. Because of faster elimination time, excellent tissue penetration, shorter half- life, low MRT after intramuscular administration of enrofloxacin at a dose rate of 5 mg⋅kg-1, it is recommended for use in yaks at therapeutic dose. 

The objective of the study was to evaluate the antiglaucoma effect of calcium channel blockers diltiazem and verapamil. Albino rabbits were used and chronic glaucoma was induced in them using freshly pre-pared 150 units of alpha–chymotrypsin. 0.1 mL of drug solution was administered topically into the left eye whereas the right served as control. The pressure recording was carried out at 15, 30, 45, 60, 90, 120, 180, 240, 300, 360 and if required at 420 and 480 min after drug instillation. Acute glaucoma was induced using 5% glucose solution administered intravenously, through the marginal ear vein, at a dose of 15 mL/kg body weight. The Intraocular Pressure (IOP) was recorded with a Schiotz-type indentation tonometer, which was previously calibrated by an open manometric calibration procedure. Topical ad-ministration of diltiazem (1%) (37.8 ± 0.632456 to 24.48 ± 0.6531) and verapamil (0.125%) (38.95 ± 1.40 to 22.85 ± 0.43) significantly reduced the elevated IOP (>30 mmHg) in alpha chymotrypsin induced chronic glaucoma model and diltiazem (1%) and verapamil (0.125%) prevented acute rise in the intraocu-lar pressure induced by intravenous administration of 5% glucose. Verapamil and diltiazem have IOP low-ering effect and can be utilized as potential investigative antiglaucoma drugs.

Allium cepa bulbs were grown in pure tap water (group I), in seven concentrations of acetaminophen (7.81, 15.62, 31.25, 62.50, 125, 250, 500, and 1000 ppm) in the presence (group II) and absence of myrobalan (fruit of Terminalia chebula) at a fix concentration of 0.10 mg/mL. Parameters of study were mean root length, mitotic index, abnormal mitosis and chromosomal aberrations and morphology of root. Aceta-minophen at all concentrations except 1000 ppm where roots did not grow at all, significantly inhibited root growth and declined mitotic index, effect appeared concentration dependent (group II). In the presence of myrobalan (group III) acetaminophen-induced mitodepression could be checked significantly. No morphological i.e. shape and color changes, abnormal mitosis and any type of chromosomal aberrations could be detected in any group. Probable protective role of myrobalan is discussed.

The effect of alcoholic extracts of leaf from Araucaria bidwillii Hook. [ABH] (Family: Araucariaceae) was evaluated in experimental models of pain and inflammation. Oral administration of 100, 200 and 300 mg/kg of leaf extracts of ABH were used for the above study. The leaf extract at 300 and 200 mg/kg showed significant reduction in acetic acid induced writhings in mice with a maximum effect of 65.1% reduction at 300 mg/kg dose. In hot plate method the percentage of pain inhibition was found to be 81.69% and 66.1% with both the tested dose of the leaf extract respectively. The effect produced by the alcoholic extract at the highest dose was comparable to that of acetyl salicylic acid at 100 mg/kg (91.52%). The alcoholic extracts of A. bidwillii showed significant inhibition in carrageenan (18.61%, 32.12% and 45.64%) and serotonin (32.81%, 38.68% and 40.75%) induced hind paw oedema in rats at 100, 200 and 300 mg/kg of the ABH extract respectively. The anti-inflammatory effects showed by the extract were comparable to that of standard indomethacin 5 mg/kg (68.51% and 63.28%). The results suggest that the anti-inflammatory and analgesic effect of the extracts as claimed in folklore medicine, which may be mediated via both peripheral and central mechanisms. 

The present study has been designed to find out the effects of forced swimming-induced oxidative stress imposition on primary and secondary sex organs and its protection by plant extract in male Wistar strain rats. This work has been designed to find out the scientific basis of the local use of the composite extract of root of Withania somnifera, leaf of Ocimum sanctum and rhizome of Zingiber officinale by village Ayurvedic doctors to protect the health disorders in connection to strenuous physical exercise, and also to search out the potentiality of above mentioned plant products on swimming-induced oxidative damage. Forced intermittent swimming for 8 hours /day for 28 days resulted a significant elevation in the level of products of free radical i.e., thiobarbituric acid reactive substances and conjugated dienes along with significant diminution in the activities of catalase, superoxide dismutase and glutathione–S–transferase in testis, prostate and seminal vesicle which were protected significantly after co-administration of methano-lic extract of said plant parts in composite manner. Testicular steroidogenesis was assessed in this condtion by measuring plasma levels of testosterone, which was diminished significantly in swimming group and was protected significantly by the composite extract of the plants parts. The antioxidative potency of this composite extract was compared with potent and standard antioxidant i.e., vitamin-E in forced swimming state. This herbal extract has no toxic effect on metabolic organs that has denoted here by the measurement of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase activities in liver and kidney. The results suggest that swimming-induced oxidative stress on male sex organs may be protected by using above mentioned medicinal plants extract. 

The present study determines the efficacy of N-acetyl cysteine (NAC) on marker enzymes, lipid peroxida-protection and antioxidants in carbon tetrachloride induced hepatotoxicity in rats. Carbon tetrachloride (CCl4) (3 mL /kg/week) administered subcutaneously to albino Wistar rats  for a period of three months significantly increased the activities of marker enzymes in plasma such as aspartate transaminase, γ-glutamyl transferase and alkaline phosphatase and increased the levels of thiobarbituric acid reactive substances and hydroperoxides in plasma and tissues (liver and kidney). A significant decrease in the levels of plasma antioxidants (glutathione, vitamin C and vitamin E) was also noted. Further, a decrease in the concentration of glutathione and the activities of superoxide dismutase, catalase and glutathione peroxidase in the tissues were observed. N-acetyl cysteine (150 mg/kg) was orally administered to normal and carbon tetrachloride-treated rats for a period of three months. N-acetyl cysteine decreased the activities of marker enzymes, lipid peroxidation and improved the antioxidant status in carbon tetrachloride-treated rats. But There were no significant alterations in these parameters in normal rats treated with N-acetyl cysteine. Histopathological observations of the liver also showed the protective effect of N-acetyl cysteine in carbon tetrachloride-induced hepatotoxicity in rats. The results of this study show the protective action of N-acetyl cysteine in carbon tetrachloride-induced hepatotoxicity in rats. This is mainly due to the effective antioxdant potential of N-acetyl cysteine. 

Cytochrome P450 2C19 (CYP2C19) plays an important role in the metabolism and elimination of a wide range of medications. The polymorphisms of this enzyme give rise to substantial inter-individual and inter-ethnic variability in drug excretion rates and final serum concentrations. For this reason, therapeutic responses and adverse drug reactions may vary from one person to another. In this study we determined genotypes of CYP2C19 in Iranian population to compare allele frequencies with previous findings in other ethnic groups. CYP2C19 (*1/*2/*3) allelic variants were determined in 200 unrelated healthy Iranian volunteers by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Six subjects (3%) were homozygous for CYP2C19*2, while 44 individuals (22%) were heterozygous. In the remainder (75%) no CYP2C19*2 was found. In addition, no CYP2C19*3 was detected in the population studied. Based on our data, there was no difference between frequency of CYP2C19 allelic variants in our study and other evaluated Caucasians (p > 0.05).

Flavonoids from Marchantia convoluta (MCF) were studied for their ability to inhibit the proliferation of 2.2.15 cells. All concentration of MCF inhibited the secretion of HBsAg and HBeAg in the cultured me-dium by 2.2.15 cells. Analysis of morphological changes of MCF-treated cells by phase-contrast micros-copy revealed a possible mode of action for MCF: inhibition of proliferation of 2.2.15 cells by inducing apoptosis.  

Objective: Succnic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic agent for the treatment of non-insulin dependent diabetes mellitus. In the present study the effect of EMS and Metformin on the activities of carbohydrate metabolic enzymes in streptozotocin–nicotinamide induced type 2 diabeteic model was investigated. Methods: EMS were injected intraperitonially at doses 2, 4, mol/g body weight (bw) respectively for 30 days, after which blood and 8 μ hemoglobin, glycosylated hemoglobin, plasma glucose and insulin, hexokinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, glucose-6-phosphate dehydrogenase in liver and glycogen in liver and muscle were assayed. Results: Glucose, glycosylated hemoglobin, glucose-6-phosphatase and fructose-1,6-bis phosphatase were significantly increased and insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase and glycogen were significantly decreased in diabetic rats. The enzyme activities were restored to the near normal levels in diabetic rats treated with EMS and Metformin. Conclusion: Our result suggest that non glucidic nutrient- EMS may act as a potent antidiabetic and insulinotropic agent by restoring the above biochemi-cal alterations in streptozotocin -nicotinamide induced type 2 diabetes.

Pathological cardiac hypertrophy was produced by partial abdominal aortic constriction (PAAC) for 4 wk, while physiological cardiac hypertrophy was produced by chronic swimming training (CST) for 8 wk in rats. Pentoxifylline (30 mg/kg, 300 mg/kg i.p., day-1) treatment was started three days before PAAC and cST and it was continued for 4 wk in PAAC and 8 wk in CST experimental model. The left ventricular (LV) hypertrophy was assessed by measuring ratio of LV weight to body weight, LV wall thickness, LV protein content and LV RNA concentration. Further venous pressure (VP) and mean arterial blood pressure (MABP) were recorded. Moreover, DNA gel electrophoresis was employed to assess the myocardial cell death. The PAAC and CST were noted to increase the ratio of LV weight to body weight, LV wall thickness, LV protein content and LV RNA concentration. Further PAAC but not CST significantly increased VP, MABP and LV necrotic cell death. Pentoxifylline, a TNF-α inhibitor markedly attenuated  PAAC induced increase in LV hypertrophy, VP, MABP and LV necrotic cell death; but it did not modulate CST induced LV hypertrophy. These results implicate TNF-α in PAAC induced cell death and pathological cardiac hypertrophy. However, TNF-α may not be involved in CST induced physiological cardiac hypert rophy.

Sodium valproate has been widely used by man as an antiepileptic drug. Hair loss and curly hair is a rare side effect of sodium valproate. We have conducted a prospective clinical study in the Department of Neurology in Shafa Hospital, Kerman, Iran for ten years (1994-2004). All 211 epileptic patients in our study were given sodium valproate as a single drug treatment. During the course of therapy, all patients were strictly monitored every 3 months. Six cases (3.5% of valproate user population) of hair loss and curling monitored every 3 months. Six cases (3.5% of valproate user population) of hair loss and three were male. This side effect observed at least 3 months after its first initial drug therapy. The estimated frequency of curly hair along with hair loss in our study is lower than previously-reported frequencies (6-12%).

There are a few reports of seizure induced by tramadol at therapeutic dose. Two case reports of repeated seizures with following agitation due to treatment with tramadol are presented here. Both of them have similar presentation and tramadol was injected intravenously at therapeutic doses. Tramadol prescription especially intravenously can evoke seizure with agitation or even status epilepticus. Tramadol should be cautiously prescribed especially for patients with history of epilepsy, addiction and old ages.

A large number of global population suffers from any one of the disorders of nervous system [ 1]. This resulted in investigation of pathophysiological factors behind the various neurological disorders and their complications, leading to the development of drugs and treatment modules. ‘Neuropharmacology deals with the action of drugs upon various parts and elements of nervous system [ 2], which broadly constitute pharmacotherapy of psychiatric disorders, epilepsies, migraine, Alzheimer’s disease, Parkinson’s disease, pain, drug / alcohol addiction and neurodegenerative disorders. Generally, all the drugs acting on the central nervous system (CNS) produces either stimulation or depression by modifying some steps in chemical synaptic transmission. In fact, these drugs were the first to be discovered and are still widely used group of drugs [ 3]. Recently, the molecular understanding of multi-subunit structures of receptors or transmitters and availability of cell based screens to identify receptor sub type selective drugs have improved the therapeutic specificity and minimized the side effects of drugs [ 4].