复方盐酸二甲双胍胶囊人体生物等效性研究

目的评价国产的复方盐酸二甲双胍胶囊(试验制剂)与市售的盐酸二甲双胍片联合格列本脲片(参比制剂)的人体相对生物利用度。方法18名健康男性志愿者随机交叉口服试验制剂2粒(每粒含二甲双胍250mg,格列本脲1.25mg)或参比制剂盐酸二甲双胍片(250mg)2片、格列本脲片(2.5mg)1片。二甲双胍的血药浓度采用离子对高效液相色谱法(HPLC)测定,格列本脲的血药浓度采用高效液相色谱-质谱法(HPLC-MS)测定,计算两者的药动学参数并评价试验制剂的相对生物利用度。结果受试者单次服用试验制剂或参比制剂后,二甲双胍的主要药动学参数如下:AUC0-24分别为(5.90±1.36)和(5.95±1.35)μg·h·mL-1,AUC0-∞分别为(6.17±1.36)和(6.28±1.36)μg·h·mL-1,Cmax分别为(0.82±0.21)和(0.82±0.14)μg·mL-1,tmax分别为(1.43±0.88)和(1.54±0.98)h,相对生物利用度为(100.21±14.10)%;格列本脲的主要药动学参数如下:AUC0-16分别为(270.28±61.82)和(268.70±61.99)ng·h·mL-1,AUC0-∞分别为(287.13±61.97)和(284.17±67.85)ng·h·mL-1,Cmax分别为(62.83±10.89)和(61.44±12.11)ng·mL-1,tmax分别为(2.53±0.79)和(2.81±0.75)h,相对生物利用度为(101.67±14.54)%。结论经统计学分析,试验制剂与参比制剂的主要药动学参数之间差异无统计学意义,试验制剂与参比制剂生物等效。     

国产格列本脲和二甲双胍复方制剂在健康志愿者的药代动力学和生物等效性

目的　研究国产复方格列本脲和盐酸二甲双胍胶囊单剂量人体的药代动力学特性和生物等效性。方法　以国产格列本脲片和进口盐酸二甲双胍片为标准参比制剂,入选的20名受试者随机交叉口服单剂量试验与参比制剂,用液相色谱-质谱法测定血浆中格列本脲和二甲双胍的浓度。结果　格列本脲的药代动力学参数分别为:AUC0-t为(603.32±196.61)和(581.70±195.01) ng.h.mL-1,Cmax为(123.46±27.03)和(128.28±3.67) ng.mL-1,tmax为(2.8±0.7)和(2.6±0.6 ) h,t1/2为(6.54±1.24)和(6.89±1.73) h。二甲双胍药代动力学参数分别为:AUC0-t为(7832.97±2603.38)和(7765.52±2870.85) ng. h.mL-1,Cmax为(1377.55±476.60)和(1367.40±551.19 )ng.mL-1,tmax为(2.7±0.9)和(2.0±0.5 ) h,t1/2为(5.72±1.24)和(5.81±1.51) h。试验制剂中格列本脲的相对生物利用度为(104.82±19.27)%,二甲双胍的相对生物利用度为(107.30±46.40)%。结论 试验制剂与参比制剂具有生物等效性。     

复方盐酸二甲双胍胶囊在人体内药物动力学和生物等效性研究

目的:研究复方盐酸二甲双胍胶囊在健康男性受试者体内药物动力学和相对生物利用度。方法:20名男性受试者随机交叉口服复方二甲双胍胶囊[试验品2粒或合用格华止与格列本脲片(参比药)各1片],用HPLC方法分别测定血浆中二甲双胍和格列本脲浓度,计算药物动力学参数和相对生物利用度。结果:口服试验药或参比药后二甲双胍的Cmax分别为(1 112±350)和(1 040±340)ng/ml;tp分别为(2.5±0.7)和(2.5±0.9)h;AUC0→∞分别为(6 018.2±1 123.8)和(6 070.4±1 626.8)ng.h/ml;格列本脲的Cmax分别为(65.7±23.4)和(69.1±20.8)ng/ml;tp分别为(3.1±0.9)和(3.2±0.9)h;AUC0→∞分别为(303.2±81.8)和(318.2±92.3)ng.h/ml;二甲双胍和格列本脲的相对生物利用度分别为(102.5±17.5)%和(97.0±15.9)%。结论:统计学分析表明复方二甲双胍胶囊与联合服用格华止与格列本脲片具有生物等效性。     

盐酸二甲双胍/格列本脲复方胶囊的人体生物等效性及其药动学研究

目的:建立人血浆中盐酸二甲双胍与格列本脲的HPLC测定法,评价盐酸二甲双胍/格列本脲复方胶囊相对于格列本脲片与盐酸二甲双胍片联合应用是否具有生物等效性.方法:20名健康受试者单剂量交叉口服等剂量供试制剂或参比制剂(格列本脲5mg和盐酸二甲双胍1 000mg)后不同时间点采血,分别采用HPLC-UV,HPLC-MS检测法,测定血浆中盐酸二甲双胍及格列本脲的药物浓度,计算其药动学参数和相对生物利用度,评价两制剂的生物等效性.结果:供试制剂与参比制剂中盐酸二甲双胍AUC0-12分别为(16.25±3.50)和(16.79±3.99)mg·h·L-1,Cmax分别为(3.35±0.71)和(3.47±0.77)mg·L-1,Tmax分别为(1.9±0.3)和(1.9±0.4)h,t1/2ke分别为(2.81±0.31)和(2.79±0.33)h.供试制剂与参比制剂中格列本脲AUC0～15分别为(1.236±0.523)和(1.170±0.522)mg·h·L-1,Cmax分别为(0.258±0.075)和(0.264±0.073)mg·L-1,Tmax分别为(2.5±0.4)和(2.4±0.4)h,t1/2ke分别为(3.93±1.61)和(3.36±0.62)h.两制剂中盐酸二甲双胍及格列本脲主要药动学参数经统计学分析差异无显著性.结论:该方法简便灵敏,盐酸二甲双胍/格列本脲复方胶囊相对于格列本脲片与盐酸二甲双胍片联合应用具有生物等效性.     

复方二甲双胍胶囊在健康受试者体内的药物动力学和相对生物利用度

目的 :研究复方二甲双胍胶囊在健康受试者体内的药物动力学和相对生物利用度。方法 :2 0名男性志愿者随机交叉口服复方二甲双胍胶囊 (试验药 )或合用二甲双胍片 格列本脲片 (参比药 ) ,HPLC 紫外法和LC MS法测定人血浆中二甲双胍和格列本脲浓度 ,计算药动学参数和相对生物利用度。结果 :口服试验药和参比药后二甲双胍的Cmax 分别为1.87± 0 .36和 1.77± 0 .35mg·L-1;Tmax为 1.7± 0 .6和 1.8± 0 .5h ;AUC0 -∞ 为 8.13± 1.32和 8.6 2±1.4 7mg·L-1·h-1,格列本脲的Cmax分别为 12 9.2±5 1.4和 12 3.9± 5 0 .7μg·L-1;Tmax 为 2 .3± 0 .7和2 .6± 0 .9h ;AUC0 -∞ 为 0 .6 90± 0 .2 2 8和 0 .6 32±0 .2 11mg·L-1·h-1,以上参数在试验药和参比药之间皆无显著性差异。试验片中二甲双胍和格列本脲相对于参比药的生物利用度分别为 95 .0 %±11.5 %和 10 9.6 %± 8.8%。结论 :复方二甲双胍胶囊中二甲双胍和格列本脲与参比药相比皆生物等效     

复方盐酸二甲双胍片的人体生物等效性

目的研究试验制剂国产复方盐酸二甲双胍片与参比制剂格列本脲片、盐酸二甲双胍片的人体生物等效性。方法健康志愿者20名,随机双交叉单剂量口服2种制剂,2次服药间隔为2 wk。分别于服药后24 h内多点抽取静脉血,用RP-HPLC测定血浆中格列本脲和盐酸二甲双胍的浓度。血药浓度经3P97程序处理,用非房室模型估算药动学参数。结果试验制剂和参比制剂血浆中格列本脲的ρmax分别为(190.91±45.01)(、175.71±27.47)μg.L-1,tmax分别为(2.60±0.87)、(2.35±0.71)h,AUC0→24分别为(1 110.85±275.12)(、1 074.77±202.76)μg.h.L-1,AUC0→∞分别为(1 187.91±275.55)(、1 168.52±168.65)μg.h.L-1;二甲双胍的ρmax分别为(3.06±0.63)、(3.06±0.55)mg.L-1,tmax分别为(1.57±0.37)(、1.65±0.37)h,AUC0→12分别为(12.05±1.92)、(12.05±1.79)mg.h.L-1,AUC0→∞分别为(12.47±1.97)(、12.51±1.80)mg.h.L-1。以格列本脲和盐酸二甲双胍计算的人体相对生物利用度分别为(103.8±17.9)%和(100.7±13.0)%。结论2种制剂具有生物等效性。     

单方和复方给药后格列美脲在Beagle犬体内药物动力学的比较

目的比较复方二甲双胍格列美脲片与单方格列美脲片中的格列美脲在Beagle犬体内的药物动力学差异。方法6只Beagle随机分为2组,犬单剂量口服单方格列美脲片和复方二甲双胍格列美脲片后,利用LC-MS/MS法分析血浆中格列美脲的浓度。采用DAS 2.1.1软件对主要药物动力学参数进行计算,并用SPSS 16.0软件对其进行配对t检验和非参数检验。结果Beagle犬单剂量口服单方格列美脲片与复方二甲双胍格列美脲片的主要药物动力学参数如下:ρmax分别为(1 722.9±237.8)和(1 860.6±315.2)μg·L-1,tmax分别为(3.3±0.3)和(3.2±0.3)h,AUC0→t分别为(12 456.9±31 93.6)和(12 048.1±3 577.8)μg·h·L-1,AUC0→∞分别为(12 578.4±3 167.2)和(12 330.4±3 756.8)μg·h·L-1。经统计学检验,各药物动力学参数间无显著性差异(P>0.05)。结论复方二甲双胍格列美脲片中的格列美脲在Beagle犬体内的药物动力学过程与单方相比无显著差异。     

复方盐酸二甲双胍片的人体相对生物利用度

目的研究国产复方盐酸二甲双胍片(含盐酸二甲双胍和格列本脲)与盐酸二甲双胍片和格列本脲片的人体相对生物利用度。方法采用随机交叉、自身对照试验设计,18名健康男性志愿者单剂量口服复方盐酸二甲双胍片(含盐酸二甲双胍500 mg,格列本脲2.5 mg)或同时口服盐酸二甲双胍片500 mg和格列本脲片2.5 mg,在不同时间点取静脉血,盐酸二甲双胍血药浓度采用HPLC-UV测定,格列本脲血药浓度采用HPLC-MS测定。以方差分析对主要药动学参数进行差别检验,以双单侧t检验进行生物等效性判定。结果单剂量口服复方盐酸二甲双胍片(含盐酸二甲双胍500 mg,格列本脲2.5 mg)或同时服用盐酸二甲双胍片500 mg和格列本脲片2.5 mg后,盐酸二甲双胍的药动学参数:AUC0~24分别为(6 252.9±2 628.3)、(6 270.6±2 202.6)ng.h.mL-1,AUC0~∞分别为(6 764.4±2 895.2)、(7 195.1±4 153.1)ng.h.mL-1,Cmax分别为(1 082.4±348.2)、(1 111.0±343.3)ng.mL-1,tmax分别为(1.5±0.5)、(1.7±0.6)h。试验制剂中盐酸二甲双胍的相对生物利用度为99.72%±13.59%。格列本脲的药物动力学参数AUC0~36分别为(533.5±247.0)、(495.7±223.3)ng.h.mL-1,AUC0~∞分别为(578.8±263.8)、(525.4±253.5)ng.h.mL-1,Cmax分别为(94.1±19.1)和(87.39±20.72)ng.mL-1,tmax分别为(1.8±0.4)和(1.9±0.4)h。与参比制剂相比,试验制剂中格列本脲的相对生物利用度为103.83%±12.94%。方差分析结果表明试验制剂与参比制剂的主要药物动力学参数之间无明显差异,双单侧t检验结果表明试验制剂与参比制剂为生物等效制剂。结论复方盐酸二甲双胍片与同时口服相同剂量的盐酸二甲双胍片和格列本脲片生物等效。     

二甲双胍格列吡嗪片人体生物等效性研究

目的:评价二甲双胍格列吡嗪片复方制剂与两种单方制剂盐酸二甲双胍片和格列吡嗪片的生物等效性。方法:采用双周期自身交叉试验设计,24名健康男性受试者分别单剂量口服二甲双胍格列吡嗪片和盐酸二甲双胍片加格列吡嗪片,并于给药前及给药后不同时间点采集肘静脉血。采用高效液相色谱-质谱方法分别测定血浆中二甲双胍和格列吡嗪的浓度。结果:受试制剂与参比制剂中二甲双胍的Cmax分别为(1 470.75±441.55)和(1 618.63±554.58)μg.L-1,tmax分别为(2.79±1.37)和(2.63±1.24)h,t1/2分别为(5.80±1.38)和(6.24±1.14)h;AUC0-tn分别为(9 699.83±2 619.73)和(10 180.88±2 559.62)μg.h.L-1,AUC0-∞分别为(10 095.41±2 681.73)和(10 616.67±2 616.83)μg.h.L-1,受试制剂的相对生物利用度F0-tn、F0-∞分别为(97.18±23.26)%和(96.83±22.43)%;格列吡嗪的Cmax分别为(251.25±61.94)和(240.13±52.43)μg.L-1,tmax分别为(3.35±1.22)和(3.38±1.35)h,t1/2分别为(4.85±1.39)和(5.08±1.76)h;AUC0-tn分别为(1 561.44±475.73)和(1 588.82±507.40)μg.h.L-1,AUC0-∞分别为(1 664.13±580.08)和(1 704.93±647.89)μg.h.L-1,受试制剂的相对生物利用度F0-tn、F0-∞分别为(100.73±19.66)%和(100.59±19.70)%。结论:受试制剂和参比制剂具有生物等效性。     

国产格列本脲和二甲双胍复方制剂在健康志愿者的药动学和相对生物利用度

目的:比较国产格列本脲和二甲双胍复方制剂在健康志愿者的药动学和相对生物利用度。方法:20例受试者随机交叉单剂量口服国产格列本脲和二甲双胍复方制剂(盐酸二甲双胍:格列本脲=500 mg:5 mg,简称试验制剂)与格列本脲片和盐酸二甲双胍片2个相同剂量单药(简称参比制剂),用液相色谱-质谱法和高效液相色谱法测定血清中格列本脲和二甲双胍的浓度。结果:试验与参比制剂中格列本脲的药动学参数分别为:AUC0-t为(1 184．8±369．4)和(1 110．5±437.2)μg·h·L-1,Cmax为(211．8±57．8)和(176．7±46．0)μg·L-1,Tmax为(3．38±0．94)和(3．43±1．03)h;2种制剂中二甲双胍药动学参数分别为:AUC0-t为(7 219．8±1 964．6)和(7 376．8±2 060．2)μg·h·L-1,Cmax为(924．7±206．2)和(1 01 1．9±331．7)μg·L-1,Tmax为(3．60±1．20)和(3．55±1．09)h。试验制剂中格列本脲和二甲双胍的相对生物利用度分别为(109．5±17．0)％和(105．2±33．4)％。结论:国产格列本脲和二甲双胍复方制剂与组成复方的2个相同剂量单药的药动学比较显示相同的相对生物利用度。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.