title: The central analgesia induced by antimigraine drugs is independent from Gi proteins: superiority of a fixed combination of indomethacin, prochlorperazine and caffeine, compared to sumatriptan, in an in vivo model.
abstract: A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1 mg/kg, prochlorperazine 1 mg/kg and caffeine 3 mg/kg, s.c.) and sumatriptan (20 mg/kg, s.c.) exert their central antinociceptive action independently from the Gi proteins. In addition, the antinociceptive efficacy of Indoprocaf in this study was statistically superior to that of sumatriptan. This study also showed that the single active ingredients of Indoprocaf, indomethacin (1 mg/kg, s.c.), prochlorperazine (1 mg/kg, s.c.) and caffeine (3 mg/kg, s.c.), were able to exert their central antinociceptive action independently from the Gi proteins. However, Indoprocaf at analgesic doses was able to abolish almost completely the abdominal constrictions, with a statistically higher efficacy compared to the single active ingredients, showing an important synergic effect of Indoprocaf. This synergic effect was evident not only when Gi proteins activity was abolished by PTX, but also under control condition, when Gi proteins were active. This study suggests that the central antinociceptive action induced by antimigraine drugs is independent from Gi proteins.
authors.affiliation: Department of Pharmacology, University of Florence, Viale G. Pieraccini, 6, 50139 Florence, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.forename: Elisa
authors.initials: E
authors.lastname: Vivoli
authors.forename: Irene
authors.initials: I
authors.lastname: Grazioli
authors.forename: Carla
authors.initials: C
authors.lastname: Uslenghi
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008881:Migraine Disorders / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D011346:Prochlorperazine / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D004338:Drug Combinations; C524793:Indoprocaf; D017366:Serotonin Receptor Agonists; D002110:Caffeine; D018170:Sumatriptan; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007213:Indomethacin; D011346:Prochlorperazine