Characterization of the interaction of pentazocine and tripelennamine: drug discrimination and mu-receptor binding assay

Abuse of the combination of pentazocine (P) and tripelennamine (T) reputedly produces an opiate-like euphoria not obtainable from either drug alone. To determine if this effect is related to interactions at the behavioral or receptor levels we tested this combination in rats trained to discriminate morphine from saline and in mu-receptor binding assays. Displacement of 3H-DHM was compared in morphine-naive, dependent and withdrawn states to determine the importance of prior morphine exposure. The morphine training cue (3 mg/kg) generalized to P but not to T. Combinations of T (0.3 and 1.0 mg/kg) with "no effect" doses of P (1 and 3 mg/kg) resulted in greater than additive increases in morphine-like responding. 3H-DHM was displaced by P but not T in naive, dependent and withdrawn states. Specific dose combinations of T (1 nM) with P (1 nM, 10 nM, 100 nM) resulted in enhanced displacement of 3H-DHM and was not related to prior morphine exposure. We conclude that the addition of T to P increases the mu-like subjective effects of P and this effect may be due to enhanced affinity of P for the mu-receptor.     

Involvement of hypothalamic neuropeptide Y in pentazocine induced suppression of food intake in rats

The potent orexigenic peptide neuropeptide Y (NPY) has been considered as a possible endogenous ligand for a subpopulation of sigma receptors (SigR). However, their mutual interaction with reference to feeding behavior remains poorly understood. In the present study, we explored the possible interaction between sigma1 receptors (Sig1R) agonist, pentazocine, and NPY on food intake in satiated rats. While pentazocine dose-dependently reduced the food intake, NPY significantly increased it at 2, 4 and 6 h post injection time points. In combination studies, pretreatment with NPY (0.1 nmol/rat, intra-PVN) normalized the inhibitory effect of pentazocine (60 μg/rat, intra-PVN) on food intake. Similarly, pre-treatment with pentazocine (30 μg/rat, intra-PVN) significantly antagonized the orexigenic effect of NPY (0.5 and 1.0 nmol/rat, intra-PVN). Moreover, pentazocine treatment decreased NPY immunoreactivity in arcuate (ARC), paraventricular (PVN), dorsomedial (DMH) and ventromedial (VMH) nuclei of hypothalamus. However, no change was observed in lateral hypothalamus (LH). Study implicates the reduced NPY immunoreactivity for the anorectic effect observed following pentazocine injections. Therefore, the concomitant activation of the NPYergic system along with the Sig1R agonist treatment may serve a useful purpose in the management of the unwanted side effects related to energy homeostasis.     

喷他佐辛复合舒芬太尼在妇科腹腔镜手术中的应用价值

目的探讨喷他佐辛复合舒芬太尼应用于妇科腹腔镜手术的价值。方法选取我院2012年3月至2013年3月收治的妇科腹腔镜手术患者120例,随机分为对照组和观察组各60例,两组患者均给予腹腔镜手术进行治疗。对照组患者采用喷他佐辛复合芬太尼方式进行麻醉,观察组采取喷他佐辛复合舒芬太尼方式进行麻醉,比较两组麻醉的临床效果。结果观察组麻醉效果明显优于对照组,差异有统计学意义(P<0.05)。结论喷他佐辛复合舒芬太尼适合妇科腹腔镜手术患者使用,值得临床推广。     

Blockade of dopamine D1 receptors by SCH 23390 antagonizes discriminative stimulus effects of pentazocine

The purpose of this investigation was to test the hypothesis that the discriminative stimulus properties of pentazocine are mediated through an interaction with dopamine receptors. Rats were trained to discriminate s.c. injections of pentazocine (3.0 mg/kg) from vehicle in a two-choice discrete trial avoidance paradigm. SCH 23390 (0.003–0.056 mg/kg), a selective antagonist of dopamine D₁ receptors, inhibited the discriminative stimulus effects of pentazocine in a dose-dependent fashion, whilst the selective D₂ receptor antagonist sulpiride (20.0–80.0 mg/kg) did not antagonize them. It appears that the dopamine D₁ receptors play an important role in the discriminative stimulus effects of pentazocine.     

Pentazocine,cyclazocine, and nalorphine as discriminative stimuli

Pentazocine, cyclazocine, and nalorphine are narcotic antagonists that also have analgesic activity of their own. the present investigation compared the stimulus properties of these three drugs in rats. Each drug was used as a discriminative stimulus for a separate group of rats. Depression of one lever resulted in food reinforcement following the administration of drug, and the opposite lever was reinforced after saline. Each drug readily acquired control of discriminated responding. The specific narcotic antagonist, naloxone, which antagonizes many of the effects of pentazocine, cyclazocine, and nalorphine, also antagonized the discrimination of these drugs. Stimulus generalization tests to each other narcotic antagonist, d-amphetamine, morphine, and LSD, showed that each narcotic antagonist has highly specific stimulus properties. Clear generalization occurred only to pentazocine and cyclazocine in the nalorphine-saline group, but neither cyclazocine nor pentazocine generalized to nalorphine.     

不同剂量喷他佐辛用于乳腺癌术后自控镇痛的效果比较

目的 比较不同剂量喷他佐辛用于乳腺癌患者术后静脉镇痛的临床效果和安全性,以探讨合适的镇痛剂量.方法 选择乳腺癌手术患者90例(ASAⅠ～Ⅱ级),随机分为三组,每组30例,P1组喷他佐辛术后镇痛剂量为0.04 mg/(kg·h),P2组为0.05 mg/(kg·h),P3组为0.06 mg/(kg·h).分别于术后4、12、24、48 h记录视觉模拟评分(VAS评分)、Prince-Henry评分、镇静评分、平均动脉压(MAP)、心率(HR)、呼吸频率(RR)、脉搏氧饱和度(SpO2).并于48 h后记录镇痛总体满意度评分和不良反应(恶心、呕吐、皮肤瘙痒).结果 P1组各时间点的VAS评分与P2、P3组比较差异有统计学意义(P<0.05);P1组4、12、24 h的Prince-Henry评分与P2、P3组比较差异有统计学意义(P<0.05);P3组4 h的镇静评分与P1组比较差异有统计学意义(P<0.05);P3组4 h的RR与P1、P2组比较差异有统计学意义(P<0.05);P1组的镇痛满意度评分与P2、P3组比较差异有统计学意义(P<0.05),P2组与P3组比较差异无统计学意义(P>0.05).结论 乳腺癌患者术后静脉持续输注0.05 mg/(kg·h)喷他佐辛,可提供较好的镇痛效果,且不良反应少. Abstract： Objective To compare the clinical effect and safety of different dose of pentazocine for postoperative patient-controlled intravenous analgesia after resection of breast cancer. Methods A total of 90 patients of ASAⅠ-Ⅱundergoing resection of breast cancer were randomly divided into 3 groups(n=30/group). Group P1 was administered with continuously intravenous pentazocine at 0.04 mg/(kg·h) after operation, group P2 pentazocine 0.05 mg/(kg·h) and group P3 pentazocine 0.06 mg/(kg·h).Visual analogue scale(VAS), Prince-Henry, sedation scores and vital signs(MAP, HR, RR, SpO2) were assessed after 4,12,24,48 hours of postoperative analgesia. The scores of satisfaction of postoperative analgesia and the adverse reactions including nausea, emesis, pruritus and resperitory inhibition were recorded after 48 hours of postoperative analgesia.Results After 4,12,24 and 48 hours of postoperative analgesia, VAS scores were higher in group P1 than that in group P2 and group P3(P<0.05).After 4,12 and 24 hours of postoperative analgesia, Prince-Henry scores were higher in group P1 than that in group P2 and group P3(P<0.05).After 4 hours of postoperative analgesia, sedation scores were higher in group P3 than that in group P1(P<0.05).After 4 hours of postoperative analgesia, RR was slower in group P3 than that in group P1 and group P2(P<0.05). The scores of satisfaction of postoperative analgesia were higher in group P1 than that in group P2 and group P3(P<0.05), there was no significantly difference in group P2 and group P3(P>0.05).Conclusions Pentazocine 0.05 mg/(kg·h) for postoperative analgesia after resection of breast cancer provides better analgesia effect and few adverse reaction.     

喷他佐辛超前镇痛在人工流产术中的应用

目的探讨喷他佐辛超前镇痛复合丙泊酚静脉全麻在人工流产术中的作用。方法175例ASAI级全麻下人工流产患者,随机均分为5组。P10组、P5组和P1组分别于麻醉前10分钟、5分钟和1分钟静脉注射喷他佐辛30mg,F组于术前10分钟静脉注射芬太尼1μg／k,C组为对照组。各组均静脉注射丙泊酚2mg／kg作全麻诱导,术中出现体动追加丙泊酚1mg／kg。观察各纽术中血压、心率及血氧饱和度。记录丙泊酚总用、麻醉诱导时间、唤醒时间和定向力恢复时间及丙泊酚注射、术中患者体动、呼吸抑制和术后恶呕发生情况。术后作VAS评分及患者满意度调查。结果研究组术中血压、心率、丙泊酚总用量、丙泊酚注射痛发生率、患者术中体动发生率、唤醒时间和定向力恢复时间较C组显著降低或缩短。F组术中呼吸抑制发生率显著高于其余4组。VAS评分,P5组和P1组显著高于C组,而P10组与F组相似（P〉0．05）,但显著低于P5组和P1组（P〈0．05）。P10组术后患者满意度显著优于其余4组。结论喷他佐辛30mg超前镇痛用于人工流产术与芬术尼1μg/kg具有相似的镇痛效果,而无芬太尼的呼吸抑制作用,其较佳的给药时机为术前10分钟。     

喷他佐辛超前镇痛在腹腔镜胆囊切除术中的应用

目的观察喷他佐辛对腹腔镜胆切除术（Lc）是否具有超前镇痛作用。方法将60例择期LC患者（ASA分级Ⅰ～Ⅱ级）随机分为研究组和对照组。观察24h内恶心、呕吐、瘙痒等不良应的发生率。研究组在全麻诱导前静脉缓慢推注喷他佐辛0．5mg／kg。对照组给予生理盐水推注。记录自主呼吸恢复时间、睁眼时间、拔管时间及术后1、2．4、8、12、24h的疼痛程度并进行评价。结果两组呼吸恢复时间、睁眼时间、拔管时间差异无统计学意义（P〉0．05）;研究组疼痛程度明显低于对照组（P〈0．05）;术后患者的并发症的发生情况差异无统计学意义（P〉0．05）。结论术前应用喷他佐辛0．5mg／kg能有效减轻腹腔镜胆囊切除术的术后疼痛,起到超前镇痛作用,是一种理想的长效中枢性镇痛方法。     

芬太尼和喷他佐辛、布托啡诺用于术后镇痛作用比较

目的:观察和比较芬太尼和布托啡诺或喷他佐辛联合用于患者术后静脉自控镇痛(PCIA)的效果。方法:90例硬膜外麻醉术后患者随机分为芬太尼镇痛泵组(Ⅰ组),芬太尼和布托啡诺镇痛泵组(Ⅱ组)及芬太尼和喷他佐辛镇痛泵组(Ⅲ组),每组30例。比较术后镇痛效果和不良反应。结果:三组均获得了满意的术后镇痛效果。VAS疼痛评分各时间段均≤3分。术后24h排尿困难和不良反应比较:Ⅲ组明显少于Ⅰ组(χ2=5.0909和χ2=4.5652,分别P<0.05)。镇静评分(OAA/S值):Ⅱ组分别大于Ⅰ组和Ⅲ组(t=2.3767和t=2.5471,分别P<0.05)。结论:芬太尼和布托啡诺或芬太尼和喷他佐辛联合用于患者PCIA效果确切,安全可靠,在药理作用方面可以取长补短。     

喷他佐辛应用于神经外科开颅手术术后镇痛效果的观察

目的：随机双盲对比观察不同剂量的喷他佐辛用于颅脑术后的镇痛效果及不良反应。方法：择期全麻颅脑手术患者90例（ASAⅠ～Ⅱ）,将其随机分为喷他佐辛90 mg组（Ⅰ组,n=30）、120 mg组（Ⅱ组,n=30）和150 mg组（Ⅲ组,n=30）。术中吸入七氟烷行全身麻醉。根据分组向患者自控镇痛泵（PCA）中注入喷他佐辛,并均以生理盐水稀释到100 ml,设置背景剂量1.5 ml/h,单次剂量0.5 ml,间隔时间15 min。术中缝硬膜时接上电子镇痛泵实行静脉自控镇痛（patient controlled intravenous analgesia,PCIA）。记录术后清醒时、4 h、16～20 h、24 h、40～44 h、48 h、64～68 h、72 h的平均动脉压（MAP）、心率（HR）、呼吸（R）、血氧饱和度（SpO2）、VAS评分、疼痛部位、疼痛性质、PCA累积总量、PCA按压用量、累计按压次数及累计有效按压次数,观察恶心、呕吐、皮肤瘙痒、呼吸抑制、颜面水肿及球结膜水肿的发生情况。结果：Ⅱ、Ⅲ组患者的PCIA按压次数、有效按压次数明显低于Ⅰ组（P〈0.05）。Ⅱ、Ⅲ组患者术后24 h内补救用药的使用例数明显少于Ⅰ组（P〈0.05）。结论：颅脑术后3 d内采用PCA持续泵注喷他佐辛120 mg（平均用量1.79 mg/h）和150 mg（平均用量2.25 mg/h）均能到达满意的术后镇痛效果,而前者的量效比更为合理。