Polish journal of pharmacology最新文献

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Is there any future for felbamate treatment? 非胺酸盐治疗有未来吗?
Polish journal of pharmacology Pub Date : 2004-05-01
Kinga K Borowicz, Barbara Piskorska, Zaneta Kimber-Trojnar, Robert Małek, Grzegorz Sobieszek, Stanisław J Czuczwar
{"title":"Is there any future for felbamate treatment?","authors":"Kinga K Borowicz,&nbsp;Barbara Piskorska,&nbsp;Zaneta Kimber-Trojnar,&nbsp;Robert Małek,&nbsp;Grzegorz Sobieszek,&nbsp;Stanisław J Czuczwar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Felbamate (2-phenyl-1,3-propanediol dicarbamate), a representative of novel antiepileptic drugs (AESs), proved to have broad-spectrum anticonvulsive activity. Particularly beneficial efficacy was found against partial seizures and Lennox-Gastaut syndrome. Therefore, felbamate started to be indicated not only as an adjunctive antiepileptic drug but also in monotherapy. Unfortunately, it was also evidenced that the drug may induce aplastic anemia or hepatic failure. The former complication was frequently described in patients with previously diagnosed hematopoetic disturbances. Thirty-four cases of well-documented bone marrow suppression, occurred fatal in thirteen cases. Subsequently, felbamate's usage was essentially restricted and at present felbamate is not a first-line AED. However, excluding anemia-prone individuals, new possibilities may open for felbamate position in add-on therapy of drug-resistant epilepsy. Experimental studies provide a good theoretical basis for this kind of treatment.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"289-94"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24580737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antidepressants in chronic unpredictable mild stress (CUMS)-induced deficit of fighting behavior. 抗抑郁药治疗慢性不可预知轻度应激(CUMS)引起的战斗行为缺陷。
Polish journal of pharmacology Pub Date : 2004-05-01
Grazyna Ossowska, Zofia Danilczuk, Bozena Klenk-Majewska, Leszek Czajkowski, Iwona Zebrowska-Łupina
{"title":"Antidepressants in chronic unpredictable mild stress (CUMS)-induced deficit of fighting behavior.","authors":"Grazyna Ossowska,&nbsp;Zofia Danilczuk,&nbsp;Bozena Klenk-Majewska,&nbsp;Leszek Czajkowski,&nbsp;Iwona Zebrowska-Łupina","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chronic unpredictable stress (CUS) is one of the behavioral models resembling in some respects (loss of normal aggresiveness) human depression. In the present study, consistent with the ethical principles for scientific experiments on animals, we have decided to modify the CUS procedure. In this new modified model named chronic unpredictable mild stress (CUMS), we have introduced mild stressor (14 h period of 45 degrees cage tilt) instead of one severe stressor (20 s exposure to electric footshock). The purpose of the present study was to determine whether this new procedure CUMS, similarly to CUS, affected the footshock-induced fighting behavior. We have also investigated the effect of antidepressant drugs with different pharmacological profiles (imipramine, mianserin, fluoxetine, moclobemide, tianeptine) and anxiolytic drug (oxazepam) on fighting behavior in rats submitted to CUMS. It was found that in rats subjected to CUMS procedure the number of fighting attacks was significantly reduced (by about 80%). Prolonged treatment (once daily, for 14 days) with imipramine (10 mg/kg/day), tianeptine (12.5 mg/kg/day), mianserin (10 mg/kg/day), moclobemide (50 mg/kg/day), fluoxetine (10 mg/kg/day), but not oxazepam (5 mg/kg/day) prevented the deficit in fighting behavior in rats subjected to CUMS. In conclusion, the results of the present study indicate that CUMS, similarly to CUS procedure, induced behavioral deficit in rats which was normalized by antidepressants with a different pharmacological profile.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"305-11"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24582435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of antagonists of adrenergic and cholinergic receptors on ion transport in the isolated rabbit caecum wall. 肾上腺素能和胆碱能受体拮抗剂对离体兔盲肠壁离子转运的影响。
Polish journal of pharmacology Pub Date : 2004-05-01
Danuta I Kosik-Bogacka, Bolesław Banach, Tomasz Tyrakowski, Tomasz Czarny, Łukasz Jodko
{"title":"Effect of antagonists of adrenergic and cholinergic receptors on ion transport in the isolated rabbit caecum wall.","authors":"Danuta I Kosik-Bogacka,&nbsp;Bolesław Banach,&nbsp;Tomasz Tyrakowski,&nbsp;Tomasz Czarny,&nbsp;Łukasz Jodko","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A hypothesis was tested in this study that antagonists of adrenergic and cholinergic receptors affect sodium and chloride ion transport in the rabbit caecum. A modified Ussing chamber was used in the experiment. It was demonstrated that isolated caecum responded to a mechanical stimulus, which consisted in gentle rinsing of the mucous surface, with changes in transepithelial electrical potential difference. An application of ion transport inhibitors, amiloride for sodium and bumetanide for chloride ions, demonstrated that both sodium and chloride ion transport in part determined the response. Pharmaceuticals that are antagonistic at neural receptors (alpha- and beta-adrenergic, nicotinic, and muscarinic), applied both for incubation and stimulation, reduced electrical potential and inhibited responses to mechanical stimuli. Basing on the results of this experiment and literature data, one can presume that analogical responses occur in vivo, and the physiological role of the autonomic system includes regulation of the thickness and consistence of mucus that separates fecal masses from the caecum walls.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"319-25"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24582437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Statins rise cytoplasmic calcium level [Ca2+]i in cultured endothelial cells. 他汀类药物提高培养内皮细胞细胞质钙水平[Ca2+]i。
Polish journal of pharmacology Pub Date : 2004-05-01
Barbara Lorkowska, Stefan Chlopicki, Ewa Marcinkiewicz, Ryszard J Gryglewski
{"title":"Statins rise cytoplasmic calcium level [Ca2+]i in cultured endothelial cells.","authors":"Barbara Lorkowska,&nbsp;Stefan Chlopicki,&nbsp;Ewa Marcinkiewicz,&nbsp;Ryszard J Gryglewski","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Recently, we have shown that some HMG-CoA reductase inhibitors (statins) induce immediate pleiotropic effects in vascular endothelium both in vivo and in vitro, to mention only PGI2-mediated thrombolysis in rats and NO-mediated endothelium-dependent vasodilation in guinea pig coronary circulation. Here we look whether immediate endothelial effect of statins is associated with mobilization of intracellular calcium ions [Ca2+]i in cultured bovine aortic endothelial cells (BAEC). We analyzed the effects of various statins (atorvastatin, cerivastatin, simvastatin, lovastatin and pravastatin at concentration of 10-30 microM) on [Ca2+]i in BAEC in comparison to responses induced by bradykinin (Bk) (10 nM), adenosine diphosphate (1 microM), acetylcholine (100 nM), adrenaline (10 microM), serotonin (10 microM) or calcium ionophore A 23187 (0.1 microM) using FURA-2 according to fluorimetric method of Grynkiewicz et al. Basal [Ca2+]i level in BAEC was between 60 and 100 nM. Bk was the most potent to induce [Ca2+]i response. Delta[Ca2+]i induced by Bk was 331.9 +/- 19.49 nM (n = 36). Delta[Ca2+]i induced by statins (30 microM), i.e. atorvastatin, cerivastatin, simvastatin, lovastatin and pravastatin were 66.4 +/- 7.38% (n = 6), 54.8 +/- 10.12% (n = 5), 58.8 +/- 13.9% (n = 8), 27.7 +/- 7.19% (n = 5) and 0% (n = 5) of the response induced by Bk (10 nM), respectively. In summary, all statins tested, except pravastatin, induce immediate increase in [Ca2+]i in endothelium. This pleiotropic activity of statins in endothelium, most likely not related to the inhibition of HMG-CoA reductase, may represent an intracellular correlate for the immediate release of NO and PGI2 by these drugs that was reported by us previously.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"313-8"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24582436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
New generation of valproic acid. 新一代丙戊酸。
Polish journal of pharmacology Pub Date : 2004-05-01
Michał K Trojnar, Ewa Wierzchowska-Cioch, Maciej Krzyzanowski, Małgorzata Jargiełło, Stanisław J Czuczwar
{"title":"New generation of valproic acid.","authors":"Michał K Trojnar,&nbsp;Ewa Wierzchowska-Cioch,&nbsp;Maciej Krzyzanowski,&nbsp;Małgorzata Jargiełło,&nbsp;Stanisław J Czuczwar","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Valproic acid (VPA) is one of four first-line antiepileptic drugs (AEDs) currently established in the long-term treatment of epilepsy. Despite VPA's wide spectrum of action, in some cases its use is limited due to specific pharmacokinetics and dangerous adverse effects. These include hepatotoxicity and teratogenecity. Such limitations account for intensive research that has been carried out in order to develop new analogues or derivatives of VPA. In our review, we focus on three out of a number of substances that have been lately under investigation: NPS 1776, valrocemide and DP-VPA. These potential AEDs present both good anticonvulsive and safety profiles and seem to be more potent than the original VPA. Clinical trials, which are now ongoing, will answer the question whether or not they could become second generation of VPA.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"283-8"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24580736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effect of sildenafil on anxiety in the plus-maze test in mice. 西地那非对小鼠加迷宫焦虑的影响。
Polish journal of pharmacology Pub Date : 2004-05-01
Mehmet Kurt, Sirri S Bilge, Elif Aksoz, Osman Kukula, Suleyman Celik, Yuksel Kesim
{"title":"Effect of sildenafil on anxiety in the plus-maze test in mice.","authors":"Mehmet Kurt,&nbsp;Sirri S Bilge,&nbsp;Elif Aksoz,&nbsp;Osman Kukula,&nbsp;Suleyman Celik,&nbsp;Yuksel Kesim","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Several studies have shown a role of nitric oxide/cyclic guanosine monophosphate signaling pathway in the regulation of anxiety. The effects of the phosphodiesterase (PDE) 5 inhibitors on anxiety are not fully understood. The aim of present study was to investigate the possible role of sildenafil, an inhibitor of cyclic GMP-specific phosphodiesterase, on anxiety in the plus-maze test in mice. Sildenafil at a dose of 0.5 mg/kg had no significant effect on the behavior in the plus-maze test but at doses of 1 and 3 mg/kg induced an anxiogenic effect. The combination of sildenafil (1 mg/kg, i.p.) and methylene blue (1 mg/kg, i.p.) abolished the anxiogenic-like effect of sildenafil. The combination of sildenafil (1 mg/kg, i.p.) and L-arginine (50 mg/kg, i.p.) decreased the percentage of time spent in open arms compared to saline-treated group. Diazepam at a dose of 2 mg/kg significantly increased the percentage of time spent in open arms (p < 0.05). Sildenafil at a dose of 3 mg/kg and the combination of L-arginine (50 mg/kg, i.p.) and sildenafil (1 mg/kg, i.p.) significantly decreased the locomotor activity (p < 0.05). These results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"353-7"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24582442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of nadroparin on bone histomorphometric parameters in rats. nadroparin对大鼠骨组织形态学参数的影响。
Polish journal of pharmacology Pub Date : 2004-05-01
Joanna Folwarczna, Waldemar Janiec, Maria Barej, Urszula Cegieła, Maria Pytlik, Ilona Kaczmarczyk-Sedlak
{"title":"Effects of nadroparin on bone histomorphometric parameters in rats.","authors":"Joanna Folwarczna,&nbsp;Waldemar Janiec,&nbsp;Maria Barej,&nbsp;Urszula Cegieła,&nbsp;Maria Pytlik,&nbsp;Ilona Kaczmarczyk-Sedlak","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Nadroparin calcium is a low-molecular-weight heparin. Low-molecular-weight heparins have a number of advantages over standard heparin (heparin), but it is not clear if low-molecular-weight heparins have less effect on bones than heparin. Administration of heparin can lead to osteoporosis. The aim of the present study was to investigate the effects of nadroparin on the rat osseous system and compare them with those of heparin. The experiments were carried out on female Wistar rats (13-15 weeks old at the beginning of the experiment), divided into 5 groups: I. Control, II. Nadroparin (1000 anti-Xa IU/kg s.c. daily), III. Nadroparin (2000 anti-Xa IU/kg s.c. daily), IV. Heparin (1000 IU/kg s.c. daily), V. Heparin (2000 IU/kg s.c. daily). Nadroparin and heparin were administered for 4 weeks. Bone mass, mineral and calcium content, macrometric and histomorphometric parameters (endosteal and periosteal transverse growth, width of endosteal and periosteal osteoid, transverse cross-section area of the cortical bone in the diaphysis and of the marrow cavity in the tibia, width of epiphyseal cartilage, width of trabeculae in the epiphysis and metaphysis in the femur) were examined. The effect of heparin on the ratio of bone mineral content to bone mass was more pronounced than that of nadroparin. Nadroparin caused unfavorable changes in the investigated bone histomorphometric parameters, similar to those caused by heparin. Nadroparin and heparin caused disorder of bone formation and intensification of bone resorption in rats.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 3","pages":"337-43"},"PeriodicalIF":0.0,"publicationDate":"2004-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24582439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effect of S-allylcysteine and lycopene in combination against N-methyl-N'-nitro-N-nitrosoguanidine-induced genotoxicity. s -丙烯基半胱氨酸和番茄红素对n -甲基-n '-硝基-n -亚硝基胍致遗传毒性的保护作用。
Polish journal of pharmacology Pub Date : 2004-03-01
Balaiya Velmurugan, Santhiyavedu T Santhiya, Siddavaram Nagini
{"title":"Protective effect of S-allylcysteine and lycopene in combination against N-methyl-N'-nitro-N-nitrosoguanidine-induced genotoxicity.","authors":"Balaiya Velmurugan,&nbsp;Santhiyavedu T Santhiya,&nbsp;Siddavaram Nagini","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Chemoprotection by diet-derived antioxidants has emerged as a cost-effective approach in preventing genotoxicity and carcinogenicity. In this study, we investigated the protective effects of S-allylcysteine (SAC) and lycopene against N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced genotoxicity. Quantification of bone marrow micronuclei and chromosomal aberrations in male Wistar rats was used to monitor the protective effects of SAC and lycopene. Intragastric administration of MNNG (40 mg/kg) induced a significant increase in the frequency of micronuclei and chromosomal aberrations. Although pretreatment with SAC and lycopene significantly reduced the frequency of MNNG-induced bone marrow micronuclei and chromosomal aberrations, the combination of SAC and lycopene exerted a greater protective effect. These findings indicate that antioxidants such as SAC and lycopene, are effective chemoprotective agents against genotoxicity and carcinogenicity especially when used in combination.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 2","pages":"241-5"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24531024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ovine model for clear-cut study on the role of cholecystokinin in antral, small intestinal and gallbladder motility. 为明确研究胆囊收缩素在胃窦、小肠和胆囊运动中的作用建立了绵羊模型。
Polish journal of pharmacology Pub Date : 2004-03-01
Krzysztof W Romański
{"title":"Ovine model for clear-cut study on the role of cholecystokinin in antral, small intestinal and gallbladder motility.","authors":"Krzysztof W Romański","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Cholecystokinin (CCK) is one of the major gastrointestinal hormones involved in the control of digestive tract and gallbladder motility. Its action involves several mechanisms. The ovine model was developed in order to further explore the role of CCK in gastric, small intestinal and gallbladder motility under various experimental conditions. Five Merino sheep were used with bipolar electrodes implanted to their antrum, entire small intestine and gallbladder as well as strain gauge force transducers were attached to the duodenum and gallbladder fundus, near the electrodes. In the course of chronic experiments, the myoelectric and motor activity were recorded by means of the adapted electroencephalograph. Among the variety of CCK-octapeptide or cerulein doses, three doses of each CCK peptide were selected and then applied for various time periods. Finally, the effects of the hormones administered within 30 s during phase 2 of the same or different migrating myoelectric complexes (MMCs) on gastrointestinal and gallbladder myoelectric and motor activity were studied in fasted and non-fasted animals. Injection of the highest dose inhibited rumination in four of the five sheep and inhibited phase 3 MMC in the antroduodenal region. Hormone administration inhibited dose-dependently antral myoelectric activity. The effects of moderate dose of both CCK peptides on myoelectric activity of the duodeno-jejunum was usually opposite (i.e. stimulatory) than that of the ileum. Gallbladder response to CCK peptides exhibited mostly the tonic character, and in some experiments, the slow wave frequency and amplitude were altered. It is concluded that CCK acts on several targets and different mechanisms underlie its multiple actions on gastrointestinal and gallbladder motility in sheep.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 2","pages":"247-56"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24531026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies. 丙咪嗪和金刚烷胺在大鼠强迫游泳试验中的协同作用。行为和药代动力学研究。
Polish journal of pharmacology Pub Date : 2004-03-01
Zofia Rogóz, Grazyna Skuza, Maciej Kuśmider, Jacek Wójcikowski, Marta Kot, Władysława A Daniel
{"title":"Synergistic effect of imipramine and amantadine in the forced swimming test in rats. Behavioral and pharmacokinetic studies.","authors":"Zofia Rogóz,&nbsp;Grazyna Skuza,&nbsp;Maciej Kuśmider,&nbsp;Jacek Wójcikowski,&nbsp;Marta Kot,&nbsp;Władysława A Daniel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Our previous studies demonstrated that joint administration of a tricyclic antidepressant drug, imipramine (IMI) with the uncompetitive antagonist of NMDA receptor, amantadine (AMA), produced stronger \"antidepressant\" effect in the forced swimming test (Porsolt's test) than the treatment with either of drugs given alone. Since it has been suggested that, in addition to their other functions, dopamine and alpha(1)-adrenergic receptors may play a role in behavioral response in the forced swimming test, in the present study we examined the effect of sulpiride (dopamine D(2/3) receptor antagonist) and prazosin (alpha(1)-adrenergic receptor antagonist) on the effect of AMA given alone or in combination with IMI in the forced swimming test in rats. We also measured the level of IMI and its metabolite, desipramine, in the rat plasma and brain, 1 h after the forced swimming test. Joint treatment with IMI (5 or 10 mg/kg) and AMA (20 mg/kg) produced stronger antidepressant-like effect than either of agents given alone. Sulpiride (10 mg/kg) or prazosin (1 mg/kg) (ineffective in the forced swimming test) inhibited an antidepressant-like effect induced by co-administration of IMI and AMA. The active behaviors in that test did not reflect an increase in general activity, since combined administration of IMI and AMA failed to enhance the locomotor activity of rats, measured in the open field test. Also sulpiride and prazosin did not decrease the exploratory activity induced by co-administration of IMI and AMA. The above result suggests that the dopamine D(2/3) and alpha(1)-adrenergic receptors may contribute to the mechanism of synergistic action of IMI and AMA in the forced swimming test in rats. The pharmacokinetic interaction can be excluded, since AMA did not change significantly the antidepressant level in the rat plasma and brain, measured 1 h after exposure to the forced swimming test.</p>","PeriodicalId":20292,"journal":{"name":"Polish journal of pharmacology","volume":"56 2","pages":"179-85"},"PeriodicalIF":0.0,"publicationDate":"2004-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24528903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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