Fundamental & clinical pharmacology
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Fundam Clin Pharmacol · Aug 2014
ReviewAntihepatitis B therapy: a review of current medications and novel small molecule inhibitors.
There are approximately 350 million hepatitis B virus (HBV) carriers worldwide. Chronic HBV infection increases the risk of liver cirrhosis and hepatocellular carcinoma. To date, two classes of antiviral drugs have been approved by the Food and Drug Administration for the treatment of hepatitis B, immunomodulators (interferon [IFN]-α and pegylated-interferon [PEG-IFN]-α) and nucleos(t)ide analogs (lamivudine, telbivudine, adefovir, tenofovir [TDF], and entecavir [ETV]). ⋯ Covering diverse chemical structures and mechanisms of action, non-nucleos(t)ide compounds offer great promise in the search for new anti-HBV drugs. This review summarizes the currently approved anti-HBV drugs and highlights advances in the identification and characterization of novel small molecule HBV inhibitors. We discuss the sources, structures, anti-HBV effects, mechanisms of action, and potential toxicities of these novel inhibitors.
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Fundam Clin Pharmacol · Aug 2014
Comparative StudyDiphenhydramine produces local cutaneous analgesia in response to dorsal skin noxious stimuli in the rat.
Although diphenhydramine has been shown to produce longer duration of spinal block than lidocaine, few studies disclose its skin infiltrative anesthesia when compared with a long-lasting local anesthetic, bupivacaine. The purpose of this study was to investigate whether diphenhydramine elicited cutaneous analgesia in comparison with bupivacaine. After inhibition of cutaneous trunci muscle reflex via subcutaneous injection of drugs in rats, we examined the local anesthetic effect of diphenhydramine and bupivacaine as infiltrative cutaneous analgesia in a dose-dependent fashion. ⋯ Neither local injection of saline nor intraperitoneal administration of a large dose of diphenhydramine or bupivacaine produced cutaneous analgesia (data not shown). We conclude that diphenhydramine is less potent than bupivacaine at producing cutaneous analgesia. At equipotent doses for infiltrative cutaneous analgesia, the duration of action of diphenhydramine is equal to that of bupivacaine.
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Fundam Clin Pharmacol · Jun 2014
Effects of tramadol on viscero-visceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis.
The effects of tramadol versus placebo administration on behavioral indicators of ureteral pain, pelvic pain and referred lumbar muscle hyperalgesia were investigated in a rat model of viscero-visceral hyperalgesia from endometriosis plus ureteral calculosis (endo + stone). Fifty female Sprague-Dawley rats underwent surgical induction of endometriosis and, 2 weeks later, were randomly assigned to five groups (10 each), to be treated i.p., twice a day, with tramadol (0.625, 1.25, 2.5, or 5 mg/kg) or saline for 5 days (14-18th day postendometriosis; prestone treatment). On the 21st day, they underwent laparotomy for stone formation in the upper left ureter (dental cement injection). ⋯ Tramadol vs. saline significantly reduced number and duration of ureteral crises, duration of pelvic behavior, and incidence of muscle hyperalgesia (P < 0.0001), with a dose-dependent effect. Prestone treatment was significantly more effective than poststone treatment for the 1.25 dose for all parameters and 2.5 dose for pelvic and muscle parameters (0.003 > P < 0.02). Tramadol, even at low doses, is thus highly protective against pain from 'viscero-visceral hyperalgesia' in endometriosis plus ureteral calculosis; it can represent a valid therapeutic approach in women with these comorbidities.
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Fundam Clin Pharmacol · May 2014
Abstracts of the 18th Annual Meeting of French Society of Pharmacology and Therapeutics, 81th Annual Meeting of Society of Physiology, 35th Pharmacovigilance Meeting, 15th APNET Seminar, 12th CHU CIC Meeting and 9th Annual Meeting of Physiology, Pharmacology and Therapeutics, 22-24 April 2014, Poitiers, France.
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Fundam Clin Pharmacol · Apr 2014
Rimantadine and 2-adamantanamine elicit local anesthesia to cutaneous nociceptive stimuli in a rat model.
The aim of this study was to investigate infiltrative cutaneous anesthesia of 2-adamantanamine and rimantadine. After subcutaneous injections of drugs in rats, the blockade of cutaneous trunci muscle reflex by 2-adamantanamine and rimantadine was evaluated. Lidocaine, a common local anesthetic, was used as control. ⋯ On an equianesthetic basis [25% effective dose (ED25 ), ED50 , and ED75 ], rimantadine and 2-adamantanamine had longer duration of action than lidocaine (P < 0.05). Neither local injection of saline nor intraperitoneal administration of a large dose of drugs elicited cutaneous anesthesia (data not shown). These data demonstrated for the first time that rimantadine had a similar potent and longer duration of skin infiltrative anesthesia than did lidocaine, whereas 2-adamantanamine had a less potency but longer duration of cutaneous anesthesia than did lidocaine.