EFFECTS OF MASSIVE DOSES OF ALPHA-MSH ON THERMOREGULATION IN THE RABBIT
EFFECTS OF MASSIVE DOSES OF ALPHA-MSH ON THERMOREGULATION IN THE RABBIT
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DOI：
10.1016/0361-9230(85)90193-5
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发表时间：
1985-01-01
影响因子：
3.8
通讯作者：
LIPTON, JM
中科院分区：
文献类型：
--
作者：
HOLDEMAN, M;LIPTON, JM
α-可以证明MSH相关化合物是临床上有用的退热剂，因为母体肽在减少发热方面是极其有效的，当口服给药时它是有效的，并且它既不刺激皮质类固醇活性，也不对人具有显著的促黑素作用。MSH可能引起有害的副作用，将其剂量大大超过退烧所需的剂量注入无发热家兔的侧脑室。100 -750 μ g α- MSH引起体温的大幅度和长时间的降低，并且剂量-反应关系在幅度和持续时间上都是钟形的。这些剂量未对动物造成明显损伤。一毫克α- MSH引起的高热反应的幅度和持续时间是可变的。先前接受大剂量α-IFN-γ的动物MSH（≥100 μ g）没有产生体温过高，甚至当给予2 mg时也是如此，表明获得了对α-β-葡聚糖的这种体温过高作用的耐受性。MSH。所有耐受或先前未注射的动物在剂量≥ 100 mg时均显示症状。1 mg α- MSH包括：流涎、激越、共济失调、呼吸窘迫和死亡增加（30%的动物）;从这些大剂量中恢复的动物恢复了外表健康的外观和行为。虽然α-当以大剂量集中给药时，MSH是有毒的，解热剂量和毒性剂量之间的5000倍差异表明，如果该肽在临床上用作解热药物，则具有宽的安全裕度。
.alpha.-MSH-related compounds may prove to be clinically useful antipyretics since the parent peptide is extremely potent in reducing fever, it is effective when given orally, and it neither stimulates corticosteroid activity nor has marked melanotropic effects in man. To determine whether or in what doses .alpha.-MSH might cause harmful side-effects, doses greatly exceeding those required to reduce fever were injected into a lateral cerebral ventricle of afebrile rabbits. One hundred-750 .mu.g .alpha.-MSH caused large and prolonged reductions in body temperature and the dose-response relation was bell-shaped for both magnitude and duration. These doses caused no apparent injury to the animals. One mg .alpha.-MSH elicited hyperthermic responses that were variable in magnitude and duration. Animals that had previously received large doses of .alpha.-MSH (.gtoreq. 100 .mu.g) did not develop hyperthermia, even when given 2 mg, indicating an acquired tolerance to this hyperthermic action of .alpha.-MSH. All animals tolerant or previously uninjected, showed symptoms with doses .gtoreq. 1 mg .alpha.-MSH that included: increased salivation, agitation, ataxia, respiratory distress and death (in 30% of the animals); those that recovered from these large doses resumed outwardly healthy appearance and behavior. Although .alpha.-MSH is toxic when given centrally in large doses, the 5000-fold difference between antipyretic and toxic doses indicates a wide safety margin should this peptide be used clinically as an antipyretic drug.