Related Experiment Video
Updated: Aug 26, 2025

Polygraphic Recording Procedure for Measuring Sleep in Mice
Published on: January 25, 2016
Melatonin synergizes with the antinociceptive effect of N-palmitoylethanolamide and paracetamol
N Alavez-Pérez1, I S Patiño-Camacho2, V Granados-Soto3
1Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México.
Abstract:
Melatonin has been shown to have an antinociceptive effect and its administration could enhance the antinociceptive effect of other drugs. This study assessed the antinociceptive effects of melatonin in combination with paracetamol and N-palmitoylethanolamide (PEA) using the formalin test in mice. Melatonin, paracetamol, and PEA were administered intraplantarly (paw) alone or combined to mice. A concentration-response curve was generated to determine the concentration needed to reach 30% of the maximal antinociceptive effect (EC30). Melatonin, paracetamol and PEA induced a concentration-dependent antinociceptive effect in both phases of the formalin test, being PEA more potent (EC30 = 7.4±0.2 mg/paw) than melatonin (EC30 = 20.5±3.1 mg/paw) or paracetamol (EC30 = 41.8±2.6 mg/paw). Combinations of melatonin with paracetamol or PEA also induced a concentration-dependent antinociceptive effect in the formalin test. Isobolographic analysis showed that melatonin interacts synergistically with either paracetamol or PEA to reduce formalin-induced inflammatory pain. However, the experimental values of EC30 were significantly smaller than those calculated theoretically.
Related Concept Videos
Sedatives and Hypnotics Drugs: Miscellaneous Agents
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
Management of Insomnia
Analgesia and Pain Management
Opioid Analgesics: Synthetic and Semisynthetic Opioids
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Sedatives and Hypnotics: Overview
Sedative-hypnotics are categorized into barbiturates, benzodiazepines (BZDs), and non-benzodiazepines or Z-drugs. These drugs work by suppressing central nervous system activity, and this suppression is dose-dependent. Older sedative medications, like barbiturates, follow a linear curve in...

