Br J Pharmacol 60(3): 445-453

C-fragment of lipotropin—an endogenous potent analgesic peptide

Abstract

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 μg.

3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 μg; 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 μg.

5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 μg/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 μg.

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 μg.

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 μg; 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).

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Selected References

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Abstract

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 μg.3 C-fragment (LPH 61-91) produced strong long-lasting analgesia when infused in a dose of 10 or 20 μg; 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 μg.5 On intravenous injection, C-fragment produced analgesia with a dose of about 200 μg/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 μg.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 μg.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 μg; 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).