Feldberg W, Smyth D G
Br J Pharmacol. 1977 Jul;60(3):445-53. doi: 10.1111/j.1476-5381.1977.tb07521.x.
1 A series of peptides derived from porcine lipotropin was examined for analgesic and other morphine-like properties on infusion into the cannulated third ventricle of cats.2 Lipotropin (LPH 1-91) itself produced no analgesia or other morphine-like effects when infused in a dose of 150 mug.3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 mug; on a molar basis the potency was between 90 and 180 times that of morphine. The following morphine-like effects were also produced: shivering leading to fever, vasodilatation of the pinnae, mydriasis, opening of the palpebral fissures, tachypnoea with bouts of panting, vocalization, hyperexcitability, restlessness and catalepsy. All the effects, including analgesia, were abolished by an intraperitoneal injection of naloxone (1 mg/kg).4 Hyperglycaemia, another central effect produced by morphine, was obtained with C-fragment infused in a dose of 60 mug.5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 mug/kg. Administered by this route, C-fragment was again more potent than morphine.6 C'-fragment (LPH 61-87), LPH 61-78 and LPH 61-69, either had no analgesic effect or produced weak short-lasting analgesia when infused in doses up to 100 mug.7 Methionine enkephalin (LPH 61-65) either produced very weak short-lasting analgesia or had no analgesic effect when infused in doses of between 30 and 400 mug.8N-methyl methionine enkephalin amide in which both termini of methionine enkephalin were protected against degradation by exopeptidases produced long-lasting analgesia when infused in doses of 150 to 180 mug; its analgesic potency was approximately 100 times less than that of C-fragment. Blocking only one terminus of methionine enkephalin did not appear to endow the peptide with analgesic properties. The N-methyl pentapeptide amide produced other morphine-like effects of which the most striking was catalepsy. All the effects were abolished by intraperitoneal naloxone (1 mg/kg).
将一系列源自猪促脂素的肽注入猫的插管第三脑室，检测其镇痛及其他类吗啡样特性。
促脂素（LPH 1 - 91）以150微克的剂量注入时，未产生镇痛或其他类吗啡样效应。
C片段（LPH 61 - 91）以10或20微克的剂量注入时，产生强烈持久的镇痛作用；按摩尔计算，其效力是吗啡的90至180倍。还产生了以下类吗啡样效应：寒战导致发热、耳廓血管舒张、瞳孔散大、睑裂张开、伴有阵发性喘气的呼吸急促、发声、过度兴奋、躁动和僵住症。包括镇痛在内的所有效应，均可通过腹腔注射纳洛酮（1毫克/千克）消除。
以60微克的剂量注入C片段时，可产生吗啡引起的另一种中枢效应——高血糖症。
静脉注射时，C片段以约200微克/千克的剂量产生镇痛作用。通过此途径给药时，C片段的效力再次强于吗啡。
C'片段（LPH 61 - 87）、LPH 61 - 78和LPH 61 - 69，以高达100微克的剂量注入时，要么无镇痛作用，要么产生微弱短暂的镇痛作用。
甲硫氨酸脑啡肽（LPH 61 - 65）以30至400微克的剂量注入时，要么产生非常微弱短暂的镇痛作用，要么无镇痛作用。
甲硫氨酸脑啡肽的两个末端均受到外肽酶降解保护的N - 甲基甲硫氨酸脑啡肽酰胺，以150至180微克的剂量注入时，产生持久的镇痛作用；其镇痛效力约比C片段低100倍。仅阻断甲硫氨酸脑啡肽的一个末端似乎并未赋予该肽镇痛特性。N - 甲基五肽酰胺产生了其他类吗啡样效应，其中最显著的是僵住症。所有效应均可通过腹腔注射纳洛酮（1毫克/千克）消除。
