Zetler G
Department of Pharmacology, Medical University of Lübeck, F.R.G.
Arch Int Pharmacodyn Ther. 1988 Nov-Dec;296:255-81.
The aporphine alkaloids bulbocapnine, corytuberine, boldine and glaucine were studied in mice and compared with haloperidol, phenobarbital and morphine. All aporphines inhibited the exploratory rearing activity and elicited palpebral ptosis, catalepsy, hypothermia, and prolonged anesthesia by thiopental. They also reduced nociception (hot plate; phenylquinone-induced writhing) and (except for corytuberine) were anticonvulsant against harman and picrotoxin, but not against bicuculline and pentetrazol; corytuberine was proconvulsant. The aporphines (except for corytuberine) antagonized the apomorphine- and methylphenidate-induced stereotyped gnawing and also the apomorphine-induced climbing activity; corytuberine was prostereotypic. The antignawing effects (including those of haloperidol) were stronger when the antagonists were administered after the agonists (gnawing full-fletched) rather than before them: this led to the speculation of a metaphilic interaction at central site(s). Clonazepam inhibited the antistereotypic effect (vs apomorphine) more potently with the aporphines than with haloperidol. The antinociceptive effect (writhing) of the aporphines was, in contrast to that of morphine, resistant to both naloxone and yohimbine. The latter applied also to the antilicking action in the hot plate test; the antijumping effect of boldine was (like that of morphine) antagonized by both yohimbine and naloxone, whereas that of corytuberine was inhibited only by naloxone and that of bulbocapnine preferentially by yohimbine. Hence, opioid and adrenergic mechanisms are unequally involved in the antinociceptive effects of the aporphines. The present results also showed that licking and jumping (in the hot plate test) are pharmacologically different phenomena. In low doses, the aporphines and haloperidol antagonized the antinociceptive effect of morphine (hot plate); hence, these drugs may be considered partial agonists or partial antagonists, respectively.
在小鼠中对阿朴啡生物碱紫堇灵、紫堇块茎碱、波尔定碱和青藤碱进行了研究，并与氟哌啶醇、苯巴比妥和吗啡进行了比较。所有阿朴啡均抑制探索性竖毛活动，并引起眼睑下垂、僵住症、体温过低以及硫喷妥钠所致麻醉时间延长。它们还减轻伤害感受（热板法；苯醌诱导的扭体反应），并且（除紫堇块茎碱外）对哈尔满和印防己毒素具有抗惊厥作用，但对荷包牡丹碱和戊四氮无抗惊厥作用；紫堇块茎碱具有惊厥作用。阿朴啡（除紫堇块茎碱外）拮抗阿扑吗啡和哌醋甲酯诱导的刻板啃咬以及阿扑吗啡诱导的攀爬活动；紫堇块茎碱具有刻板作用。当拮抗剂在激动剂之后（完全啃咬时）而非之前给药时，抗啃咬作用（包括氟哌啶醇的作用）更强：这导致推测在中枢部位存在亲代谢相互作用。氯硝西泮对阿朴啡的抗刻板作用（相对于阿扑吗啡）的抑制作用比氟哌啶醇更强。与吗啡不同，阿朴啡的抗伤害感受作用（扭体反应）对纳洛酮和育亨宾均有抗性。后者也适用于热板试验中的抗舔舐作用；波尔定碱的抗跳跃作用（与吗啡一样）被育亨宾和纳洛酮均拮抗，而紫堇块茎碱的抗跳跃作用仅被纳洛酮抑制；紫堇灵的抗跳跃作用则优先被育亨宾抑制。因此，阿朴啡的抗伤害感受作用中，阿片样物质和肾上腺素能机制的参与程度不同。目前的结果还表明，舔舐和跳跃（在热板试验中）是药理学上不同的现象。低剂量时，阿朴啡和氟哌啶醇拮抗吗啡的抗伤害感受作用（热板法）；因此，这些药物可分别被视为部分激动剂或部分拮抗剂。
