EVALUATION OF THE CNS PROPERTIES OF SCH-29851, A POTENTIAL NON-SEDATING ANTIHISTAMINE
EVALUATION OF THE CNS PROPERTIES OF SCH-29851, A POTENTIAL NON-SEDATING ANTIHISTAMINE
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DOI：
10.1007/bf01978891
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发表时间：
1984-01-01
期刊：
影响因子：
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通讯作者：
GULBENKIAN, A
中科院分区：
文献类型：
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作者：
BARNETT, A;IORIO, LC;GULBENKIAN, A
SCH 29851 [8-氯-6,11-二氢-11-(1-乙氧羰基-4-哌啶亚基)-5-H-苯并[5,6]环庚[1,2-b]-吡啶]是在寻找不影响中枢神经系统的新型抗组胺药的过程中发现的。通过抑制组胺诱导的豚鼠致死率和组胺诱导的小鼠爪水肿来评估 SCH 29851 和其他抗组胺药的抗组胺效力和作用持续时间。对可能的中枢神经系统影响的评估包括对小鼠、大鼠、狗和猴子的粗略观察，预防电击引起的惊厥、乙酸引起的扭体和毒扁豆碱引起的致死，以及与镇静作用相关的生化测量，例如体内 3H-美吡拉明在小鼠大脑和体外结合的位移3H-2[N(2,6-二甲氧基-苯氧基乙基)]氨基-甲基-1,4-苯并二恶烷[WB 4101]在豚鼠皮层中的结合。对几种被认为具有不同程度镇静作用的抗组胺药进行了比较，包括苯海拉明、异丙嗪、氯苯那敏和阿扎他定，以及据报道在拮抗组胺外周作用的剂量下对人体无镇静作用的新型抗组胺药特非那定和阿司咪唑。 SCH 29851 在使用的测试中具有抗组胺活性，其效力至少与大多数标准相当，并且在用作 CNS 活性指标的所有功能和生化模型中缺乏活性。 SCH 29851 应该是一种有效的长效抗组胺药，在治疗剂量下不会产生镇静作用。
SCH 29851 [8-chloro-6,11-dihydro-11-(1-carboethoxy-4-piperidylidene)-5-H-benzo[5,6]cyclohepta[1,2-b]-pyridine] was discovered as part of a search for a new antihistamine without effects on the CNS. Antihistaminic potency and duration of action of SCH 29851 and other antihistamines were assessed by inhibition of histamine-induced lethality in guinea pigs and histamine-induced paw edema in mice. Evaluation of possible CNS effects included gross observation of mice, rats, dogs and monkeys, prevention of electroshock-induced convulsions, acetic acid-induced writhing and physostigmine-induced lethality in mice and biochemical measures related to sedative liability such as displacement of in vivo 3H-mepyramine binding in mouse brain and in vitro 3H-2[N(2,6-dimethoxy-phenoxyethyl)]amino-methyl-1,4-benzodioxane [WB 4101] binding in guinea pig cortex. Comparisons were made to several antihistamines considered to be sedative to varying degrees, including diphenhydramine, promethazine, chlorpheniramine and azatadine and to the newer antihistamines terfenadine and astemizole which are reported to be nonsedating in man at doses that antagonize the effects of histamine peripherally. SCH 29851 had antihistamine activity in the tests used with a potency at least comparable to most standards and was devoid of activity in all the functional and biochemical models used as indices of CNS activity. SCH 29851 should be an effective, long acting, antihistamine in man without sedative effects at therapeutic doses.