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Acute Oral Administration (acute + oral_administration)
Selected AbstractsThe Novel Antioxidant, AC3056 (2,6-di-t-butyl-4-((Dimethyl-4-Methoxyphenylsilyl)Methyloxy)Phenol), Reverses Erectile Dysfunction in Diabetic Rats and Improves NO-mediated Responses in Penile Tissue from Diabetic MenTHE JOURNAL OF SEXUAL MEDICINE, Issue 2 2009Javier Angulo PhD ABSTRACT Introduction., Diabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED. Aim., To evaluate the effects of the antioxidant, AC3056 (2,6-di- t -butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED. Methods., Erectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively. Main Outcome Measures., The influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-,B (NF-,B) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined. Results., Eight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-,B expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 µM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 µM) was corrected by AC3056 (30 µM). Conclusions., These results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes. Angulo J, Peiró C, Cuevas P, Gabancho S, Fernández A, González-Corrochano R, La Fuente JM, Baron AD, Chen KS, and Sáenz de Tejada I. The novel antioxidant, AC3056 (2,6-di-t-butyl-4-([dimethyl-4-methoxyphenylsilyl] methyloxy) phenol), reverses erectile dysfunction in diabetic rats and improves NO-mediated responses in penile tissue from diabetic men. J Sex Med 2009;6:373,387. [source] Effects of a novel hydrophilic phytostanol analog on plasma lipid concentrations in gerbilsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2001Kishor M. Wasan Abstract This study was designed to determine the effects of a novel hydrophilic phytostanol analog, FM-VP4, on total plasma cholesterol, total plasma triglyceride, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations after acute oral administration to gerbils. Gerbils were administered a standard gerbil diet for 4 continuous weeks, and daily water and food intake was monitored and replaced. The diet contained either no FM-VP4 (control) or FM-VP4 at the following concentrations: 0.25, 0.50, 1.0, or 2.0% w/w; six gerbils were fed each diet formulation. After 4 weeks of receiving a single diet formulation, blood was obtained from each gerbil by cardiac puncture and the animals were sacrificed humanely. Plasma obtained from this blood was analyzed for total cholesterol, total triglyceride, and HDL cholesterol levels by standard enzymatic and precipitation techniques. LDL cholesterol levels were calculated using the Friedewald equation. Administration of dietary FM-VP4 resulted in significant decreases in total plasma cholesterol and LDL cholesterol concentrations compared with controls. Dietary FM-VP4 at concentrations of 1% and 2% (w/w) decreased total plasma cholesterol by 3.4 mmol/L compared with controls. This decrease was entirely due to the loss of cholesterol from the LDL pool because LDL cholesterol was decreased by 3.3 and 3.2 mmol/L after 1% and 2% (w/w) FM-VP4, respectively. There were no significant changes in plasma triglyceride or HDL cholesterol concentrations after the administration of FM-VP4. Animals administered 1% or 2% (w/w) FM-VP4 also had significantly lower body weight after 4 weeks of treatment compared with the other groups. However, no unusual behavior was observed in these animals. No major differences in daily water or food intake were observed throughout the study. These findings indicate that FM-VP4 decreases total and LDL cholesterol concentrations. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:1795,1799, 2001 [source] Carisbamate, a Novel Antiepileptic Candidate Compound, Attenuates Alcohol Intake in Alcohol-Preferring RatsALCOHOLISM, Issue 8 2009Amir H. Rezvani Background:, Since 1994, when naltrexone (Revia®) was approved by the FDA for the treatment of alcoholism, only 2 other drugs (Campral® and Topamax®) have been approved for alcoholism treatment. However, various experimental drugs, including antiepileptic medications, have been tested in both animal models and in humans with some promising results. The purpose of this project was to study the effect of the novel neuromodulator carisbamate, which is in development for epilepsy treatment, on alcohol intake in selectively bred alcohol-preferring rats. Methods:, Male alcohol-preferring inbred P rats were allowed to freely drink water or alcohol (10%, v/v) using a 2-bottle choice procedure. After stable baselines for alcohol and water intakes were established, the acute effects of oral carisbamate (0, 10, 30, 45, 60, and 90 mg/kg) were assessed. Then, the chronic effect of the compound (60 mg/kg/day for 14 consecutive days) on alcohol intake was assessed in a separate group of male P rats. In another set of experiments, the effects of carisbamate and naltrexone on alcohol withdrawal-induced elevated drinking of alcohol, an index of craving, were compared. Rats were withdrawn from alcohol for 24 hours and were given vehicle, 20 mg/kg naltrexone or 60 mg/kg carisbamate 30 minutes before re-exposure to alcohol. Alcohol and water intake was measured 6 hours after alcohol re-exposure. To determine the effects of carisbamate on saccharin preference, rats were put on a 2-bottle choice of water versus a solution of 2% saccharin. Then, the effect of the highest dose of carisbamate (90 mg/kg) and naltrexone (20 mg/kg) and the vehicle on saccharin preference was determined. Results:, Our results showed that there was a selective dose-dependent reduction in alcohol intake and preference in the alcohol-preferring P rat after an acute oral administration of carisbamate. There were no significant effects on food or water intake. Chronic administration of carisbamate significantly reduced alcohol intake and preference initially, but partial tolerance developed after the 10th treatment. The degree of tolerance development was less than that observed for naltrexone. Acute administration of carisbamate was more effective than naltrexone in reducing enhanced alcohol intake after a period of alcohol deprivation. Compared with control vehicle neither carisbamate nor naltrexone had a significant effect on saccharin intake and preference. Conclusion:, The novel neuromodulator compound carisbamate has a favorable profile of effects on alcohol intake and related measures and should be considered for testing on human alcoholics. [source] The Effects of Oral Administration of D-Modafinil on Male Rat Ejaculatory BehaviorTHE JOURNAL OF SEXUAL MEDICINE, Issue 1pt1 2010Lesley Marson PhD ABSTRACT Introduction., Premature ejaculation (PE) is one of the most common forms of male sexual dysfunction. Examination of various classes of drugs on ejaculation latency would provide further opportunities for drug development in this field. Aim., This study was conducted to examine the effects of the d-isomer of modafinil (d-modafinil) on ejaculatory behavior in a rat model. Methods., Male sexual behavior in the rat was examined after acute oral administration of d-modafinil (10 mg/kg, 30 mg/kg, and 100 mg/kg) in copulation studies with receptive females. Main Outcome Measures., The latency to ejaculation, post-ejaculatory interval, and the frequency of mounting behavior were measured. Results d-modafinil (30 mg/kg and 100 mg/kg) produced a significant delay in ejaculation. The delay in ejaculation was accompanied by an increase in the number of intromissions without any change in the mount or intromission latency. The possible mechanisms of action of d-modafinil to produce this delay in ejaculation are discussed. Conclusions., These results demonstrate that acute oral administration of d-modafinil can lengthen the latency to ejaculation in rats without suppressing sexual behavior. The greatest delay in ejaculation was observed in animals with shorter baseline ejaculatory latencies. Investigation into new classes of drugs that modulate ejaculation may provide new therapeutic options for treating PE. Marson L, Yu G, and Farber NM. The effects of oral administration of d-modafinil on male rat ejaculatory behavior. J Sex Med 2010;7:70,78. [source] | ||||||||||