n -烯丙基去甲他唑嗪对松鼠猴电击滴定的影响。

Alcohol and drug research Pub Date : 1987-01-01
B L Slifer, L A Dykstra
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引用次数: 0

摘要

对原型sigma激动剂n -烯丙基去甲他唑嗪的立体异构体的影响进行了评估,以训练松鼠猴对电击滴定计划作出反应。猴子按照固定的比例做出反应,以减少对尾巴的电击程度。同分异构体的效果与苯环利定和吗啡单独使用的效果以及与抑制速率剂量的吗啡联合使用的效果进行了比较。吗啡增加了维持休克的水平,但没有降低休克存在时的反应率。(+)-同分异构体和PCP都能提高猴子维持休克的水平,但仅限于某些动物。n -烯丙基去甲他唑嗪的(-)-异构体对猴子维持休克的水平要么降低,要么没有影响。同分异构体在降低应答率方面是等效的。当与吗啡联合使用时,只有(-)-异构体能拮抗吗啡增加休克水平的作用。因此,同分异构体对反应率有相似的影响,但(+)-同分异构体,如PCP,在增加猴子维持电击水平方面更有效,而只有(-)-同分异构体作为吗啡拮抗剂有效。这些结果表明n -烯丙基去甲他唑辛的(+)-异构体具有类似镇痛的作用,并证实了(-)-异构体的阿片拮抗剂特性。
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The effects of N-allylnormetazocine on electric shock titration in squirrel monkeys.

The effects of the stereoisomers of the prototypic sigma agonist N-allylnormetazocine were evaluated in squirrel monkeys trained to respond on an electric shock titration schedule. The monkeys responded on a fixed-ratio schedule to decrease the level of shock delivered to their tails. The effects of the isomers were compared to the effects of phencyclidine and morphine administered alone and also in combination with a rate-suppressing dose of morphine. Morphine increased the level at which shock was maintained without decreasing rates of responding in the presence of shock. Both the (+)-isomer and PCP produced increases in the levels at which the monkeys maintained the shock, but only in some animals. The (-)-isomer of N-allylnormetazocine resulted in either decreases or no effect on the level at which the monkeys maintained the shock. The isomers were equipotent in decreasing response rates. When tested in combination with morphine, only the (-)-isomer antagonized the shock-level increasing effects of morphine. Thus, the isomers had similar effects on response rates but the (+)-isomer, like PCP, was more effective in increasing the level at which the monkeys maintained electric shock, while only the (-)-isomer was effective as a morphine antagonist. These results suggest analgesic-like effects for the (+)-isomer of N-allylnormetazocine and substantiate the opiate-antagonist properties of the (-)-isomer.

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