CNS drug reviews最新文献

{"title":"Paracetamol: New Vistas of an Old Drug","authors":"Alfio Bertolini,&nbsp;Anna Ferrari,&nbsp;Alessandra Ottani,&nbsp;Simona Guerzoni,&nbsp;Raffaella Tacchi,&nbsp;Sheila Leone","doi":"10.1111/j.1527-3458.2006.00250.x","DOIUrl":"10.1111/j.1527-3458.2006.00250.x","url":null,"abstract":"<p>Paracetamol (acetaminophen) is one of the most popular and widely used drugs for the treatment of pain and fever. It occupies a unique position among analgesic drugs. Unlike NSAIDs it is almost unanimously considered to have no antiinflammatory activity and does not produce gastrointestinal damage or untoward cardiorenal effects. Unlike opiates it is almost ineffective in intense pain and has no depressant effect on respiration. Although paracetamol has been used clinically for more than a century, its mode of action has been a mystery until about one year ago, when two independent groups (Zygmunt and colleagues and Bertolini and colleagues) produced experimental data unequivocally demonstrating that the analgesic effect of paracetamol is due to the indirect activation of cannabinoid CB₁ receptors. In brain and spinal cord, paracetamol, following deacetylation to its primary amine (p-aminophenol), is conjugated with arachidonic acid to form N-arachidonoylphenolamine, a compound already known (AM404) as an endogenous cannabinoid. The involved enzyme is fatty acid amide hydrolase. N-arachidonoylphenolamine is an agonist at TRPV1 receptors and an inhibitor of cellular anandamide uptake, which leads to increased levels of endogenous cannabinoids; moreover, it inhibits cyclooxygenases in the brain, albeit at concentrations that are probably not attainable with analgesic doses of paracetamol. CB₁ receptor antagonist, at a dose level that completely prevents the analgesic activity of a selective CB₁ receptor agonist, completely prevents the analgesic activity of paracetamol. Thus, paracetamol acts as a pro-drug, the active one being a cannabinoid. These findings finally explain the mechanism of action of paracetamol and the peculiarity of its effects, including the behavioral ones. Curiously, just when the first CB₁ agonists are being introduced for pain treatment, it comes out that an indirect cannabino-mimetic had been extensively used (and sometimes overused) for more than a century.</p>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 3-4","pages":"250-275"},"PeriodicalIF":0.0,"publicationDate":"2007-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00250.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26492372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silperisone: A Centrally Acting Muscle Relaxant","authors":"Sándor Farkas","doi":"10.1111/j.1527-3458.2006.00218.x","DOIUrl":"10.1111/j.1527-3458.2006.00218.x","url":null,"abstract":"<div>\u0000 \u0000 <p>Silperisone is a tolperisone like organosilicon compound with centrally acting muscle relaxant properties. Studies in mice showed that silperisone may have less propensity to cause CNS depressant or motor side effects than tolperisone or other antispastic drugs. In cats and rats, silperisone was an effective suppressant of monosynaptic and polysynaptic spinal reflexes and decerebrate rigidity. Its suppressant effect on the spinal reflexes was also demonstrated in the isolated hemisected rat spinal cord <i>in vitro.</i> The <i>in vivo</i> potency and efficacy of silperisone by i.v administration were similar to those of tolperisone and eperisone. However, in cats by intraduodenal administration and in mice by oral administration its duration of action was much longer and its functional bioavailability much higher than of the other two drugs. With regard to its profile of actions silperisone was similar to tolperisone with minor differences. The most striking difference was in pontine facilitation and bulbar inhibition of the patellar reflex. Tolperisone depressed both, whereas silperisone inhibited only the former. The mechanism underlying the spinal reflex depressant effects of silperisone involves the blockade of voltage gated neuronal sodium and calcium channels leading to a decreased release of excitatory transmitter and reduced neuronal excitability. In addition, silperisone has potassium channel blocking effect, which is stronger than that of tolperisone. Silperisone is absorbed rapidly and is extensively metabolized in rats. However, its metabolism in dogs and particularly in humans is much less extensive. The elimination half-life of silperisone in humans is 12 to 16 h, so that it can be administered once or twice daily. Phase I clinical studies with silperisone at doses up to 150 mg/day failed to detect any adverse effects at plasma concentrations considered to be effective in the preclinical tests. These findings suggested that silperisone might be a useful antispastic drug. However, findings in chronic animal toxicity studies led to the discontinuation of silperisone's development.</p>\u0000 <p> \u0000 </p><div><span>(1)</span><div><picture>\u0000 <source></source></picture></div>\u0000 </div> [ Chemical structure of silperisone. ]\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 3-4","pages":"218-235"},"PeriodicalIF":0.0,"publicationDate":"2007-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00218.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26492404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of the Pharmacology and Clinical Profile of Bupropion, an Antidepressant and Tobacco Use Cessation Agent","authors":"Linda P. Dwoskin,&nbsp;Anthony S. Rauhut,&nbsp;Kelley A. King-Pospisil,&nbsp;Michael T. Bardo","doi":"10.1111/j.1527-3458.2006.00178.x","DOIUrl":"10.1111/j.1527-3458.2006.00178.x","url":null,"abstract":"<div>\u0000 \u0000 <p>Bupropion hydrochloride ((±)-2-tert-butylamino)-3′-chloropropiophenone · HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, bupropion has been shown to attenuate nicotine-induced unconditioned behaviors, to share or enhance discriminative stimulus properties of nicotine and to have a complex effect on nicotine self-administration, i.e., low doses augmenting nicotine self-administration and high doses attenuating self-administration. Current studies show that bupropion facilitates the acquisition of nicotine conditioned place preference in rats, further suggesting that bupropion enhances the rewarding properties of nicotine. Bupropion has been shown to attenuate the expression of nicotine withdrawal symptoms in both animal models and human subjects. With respect to relapse, current studies show that bupropion attenuates nicotine-induced reinstatement in rats, but large individual differences are apparent. Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent. In clinical trials, bupropion is being tested as a candidate treatment for psychostimulant drug abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is available in three bioequivalent oral formulations, immediate release (IR), sustained release (SR), and extended release (XL). Extensive hepatic metabolism of bupropion produces three pharmacologically active metabolites, which may contribute to its clinical profile.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 3-4","pages":"178-207"},"PeriodicalIF":0.0,"publicationDate":"2007-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00178.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26492368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Augmentation Treatment of Psychotherapy for Anxiety Disorders with D-Cycloserine","authors":"Stefan G. Hofmann,&nbsp;Mark H. Pollack,&nbsp;Michael W. Otto","doi":"10.1111/j.1527-3458.2006.00208.x","DOIUrl":"10.1111/j.1527-3458.2006.00208.x","url":null,"abstract":"<div>\u0000 \u0000 <p>Anxiety disorders are among the most common mental disorders. One of the most effective strategies to treat anxiety disorders is exposure therapy with or without cognitive intervention. Fear reduction in exposure therapy is similar to extinction learning. Preclinical studies suggest that extinction learning can be blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor, and facilitated with D-cycloserine (DCS), a partial agonist at the glycine recognition site of the NMDA receptor in the amygdala. DCS is an established antibiotic drug for the chronic treatment of tuberculosis in humans, but has only recently been investigated as an augmentation therapy for psychological treatment procedures. The review of the literature provides preliminary support for the use of acute dosing of DCS as an adjunctive intervention to exposure therapy for anxiety disorders, including specific phobia and social anxiety disorder. Negative results have recently been reported in the treatment of subclinical fears of animals. These studies suggest that DCS needs to be administered on an acute rather than a chronic dosing schedule, include sufficient time for memory consolidation, and be administered together with psychological treatment that leaves sufficient room for further improvement. It remains to be seen whether these highly promising findings represent reliable pharmacological strategies to enhance exposure therapy of anxiety disorders.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 3-4","pages":"208-217"},"PeriodicalIF":0.0,"publicationDate":"2007-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00208.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26492402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Profile of the 5-HT2C Receptor Agonist WAY-163909; Therapeutic Potential in Multiple Indications","authors":"John Dunlop,&nbsp;Karen L. Marquis,&nbsp;HK Lim,&nbsp;Louis Leung,&nbsp;John Kao,&nbsp;Cynthia Cheesman,&nbsp;Sharon Rosenzweig-Lipson","doi":"10.1111/j.1527-3458.2006.00167.x","DOIUrl":"10.1111/j.1527-3458.2006.00167.x","url":null,"abstract":"<div>\u0000 \u0000 <p>The 5-HT_2C receptor subtype has been implicated in a wide variety of conditions including obesity, anxiety, depression, obsessive compulsive disorder, schizophrenia, migraine and erectile dysfunction and as a consequence has received considerable attention as a target for drug discovery. Here we review the pharmacological, pharmacokinetic and toxicological profile of WAY-163909 {(7b<i>R</i>,10a<i>R</i>)-1,2,3,4,8,9,10,10a-octahydro-7b<i>H</i>-cyclopenta-[b][1,4]diazepino[6,7,1hi]indole}, a novel 5-HT_2C receptor selective agonist. Consistent with a potential therapeutic utility in obesity, schizophrenia and depression WAY-163909 was found to have robust dose-dependent effects in animal models of obesity, psychotic-like behavior or depression.</p>\u0000 </div>","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"12 3-4","pages":"167-177"},"PeriodicalIF":0.0,"publicationDate":"2007-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.2006.00167.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"26492403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Obsessional and Antidepressant Profile of Besipirdine","authors":"C. P. Smith,&nbsp;A. T. Woods-Kettelberger,&nbsp;R. Corbett,&nbsp;R. D. Porsolt,&nbsp;J. E. Roehr,&nbsp;G. M. Bores,&nbsp;A. Giovanni,&nbsp;M. R. Szewczak,&nbsp;D. K. Rush,&nbsp;L. L. Martin,&nbsp;J. T. Klein,&nbsp;D. J. Turk,&nbsp;E. M. DiLeo,&nbsp;R. C. Effland,&nbsp;F. P. Huger,&nbsp;S. Kongsamut","doi":"10.1111/j.1527-3458.1997.tb00313.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00313.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 1","pages":"1-23"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00313.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74612072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AHN649: Preclinical Evaluation of a Novel Anticonvulsant and Neuroprotective Analog of Dextromethorphan","authors":"Frank C. Tortella,&nbsp;Xi-Chun M. Lu,&nbsp;Amy H. Newman,&nbsp;Paul Britton","doi":"10.1111/j.1527-3458.1997.tb00322.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00322.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 2","pages":"168-180"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00322.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79479727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of 5-HT1A Receptors in Acquisition, Consolidation and Retrieval of Learning","authors":"Alfredo Meneses,&nbsp;Enrique Hong","doi":"10.1111/j.1527-3458.1997.tb00317.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00317.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 1","pages":"68-82"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00317.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80716878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Iloperidone: Preclinical Profile and Early Clinical Evaluation","authors":"R. Corbett,&nbsp;L. Griffiths,&nbsp;J. E. Shipley,&nbsp;U. Shukla,&nbsp;J. T. Strupczewski,&nbsp;A. M. Szczepanik,&nbsp;M. R. Szewczak,&nbsp;D. J. Turk,&nbsp;H. M. Vargas,&nbsp;S. Kongsamut,&nbsp;the Iloperidone Project Team","doi":"10.1111/j.1527-3458.1997.tb00320.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00320.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 2","pages":"120-147"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00320.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84517919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MDL 100,907: A Selective 5-HT2A Receptor Antagonist for the Treatment of Schizophrenia","authors":"Christopher J. Schmidt,&nbsp;John H. Kehne,&nbsp;Albert A. Carr","doi":"10.1111/j.1527-3458.1997.tb00316.x","DOIUrl":"10.1111/j.1527-3458.1997.tb00316.x","url":null,"abstract":"","PeriodicalId":94307,"journal":{"name":"CNS drug reviews","volume":"3 1","pages":"49-67"},"PeriodicalIF":0.0,"publicationDate":"2006-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1527-3458.1997.tb00316.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86972548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}