Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys.
Behavioral effects of the systemically active delta opioid agonist BW373U86 in rhesus monkeys.
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发表时间：
1994-09
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通讯作者：
S. Negus;E. Butelman;K. Chang;B. Decosta;G. Winger;J. Woods
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作者：
S. Negus;E. Butelman;K. Chang;B. Decosta;G. Winger;J. Woods
在恒河猴中检查了（+-）-4-（（α R*）-α-（（2S*，5 R *）-4-烯丙基-2，5-二甲基-1-哌嗪基）-3-羟基苄基）-N，N-二乙基苯甲酰胺二盐酸盐（BW 373 U86）（一种非肽类、全身活性δ阿片受体激动剂）的行为效应。BW 373 U86、μ激动剂阿芬太尼和κ激动剂U69，593 [（5 α，7 α，8 β）-（-）-N-甲基-N-（7-（1-吡咯烷基）-1-氧杂螺-（4，5）癸-8-基）苯乙酰胺]均产生剂量依赖性抑制反应速率，维持在固定比率30的食物呈现时间表下。BW 373 U 86的心率抑制作用持续1 ~ 2小时，4小时后不再明显，选择性δ受体拮抗剂纳曲吲哚（NTI）可较强地拮抗BW 373 U 86的心率抑制作用（pKB = 6.5），NTI对BW 373 U 86的拮抗作用持续约4小时，NTI对阿芬太尼的拮抗作用较弱（pKB = 5.1）和最高剂量的NTI检查（10.0 mg/kg）没有拮抗U 69，593。BW 373 U86没有推广到μ激动剂阿芬太尼或κ激动剂乙基酮环唑辛的区别性刺激作用。BW 373 U86也没有产生抗伤害性的影响，在温水尾部撤回程序，在猴子呼吸空气或5%的CO2或加强作用，在自我管理程序的呼吸抑制效果显着。检查的最高剂量BW 373 U86（1.78 mg/kg）在1只猴中引起惊厥。NTI拮抗BW 373 U86的速率抑制作用的高相对效力与BW 373 U86在恒河猴中作为全身活性的δ选择性激动剂的特征一致。在本研究中评估的条件下，BW 373 U86结合的δ受体似乎不介导猴的抗伤害感受、呼吸抑制或增强作用。
The behavioral effects of (+-)-4-((alpha R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3- hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride (BW373U86), a nonpeptidic, systemically active, delta opioid agonist, were examined in rhesus monkeys. BW373U86, the mu agonist alfentanil and the kappa agonist U69,593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro- (4,5)dec-8-yl)benzeneacetamide] all produced a dose-dependent suppression of response rates maintained under a fixed ratio 30 schedule of food presentation. The rate-suppressing effects of BW373U86 lasted 1 to 2 hr and were no longer apparent after 4 hr. The selective delta antagonist naltrindole (NTI) antagonized the effects of BW373U86 with relatively high potency (pKB = 6.5) and the antagonist effects of NTI against BW373U86 lasted approximately 4 hr. NTI was less potent in antagonizing alfentanil (pKB = 5.1) and the highest dose of NTI examined (10.0 mg/kg) did not antagonize U69,593. BW373U86 did not generalize to the discriminative stimulus effects of the mu agonist alfentanil or the kappa agonist ethylketocyclazocine. BW373U86 also did not produce antinociceptive effects in the warm-water tail-withdrawal procedure, significant respiratory depressant effects in monkeys breathing either air or 5% CO2 or reinforcing effects in a self-administration procedure. The highest dose of BW373U86 examined (1.78 mg/kg) produced convulsions in one monkey. The high relative potency of NTI to antagonize the rate-suppressing effects of BW373U86 was consistent with the characterization of BW373U86 as a systemically active, delta-selective agonist in rhesus monkeys. Under the conditions evaluated in the present study, the delta receptors to which BW373U86 binds do not appear to mediate antinociceptive, respiratory depressant or reinforcing effects in monkeys.