Pharmacological investigation of trimetazidine in models of inflammation, pain and gastric injury in rodents.
The antinociceptive, anti-inflammatory and gastric effects of trimetazidine (2,3,4-trimethoxybenzyl-piperazine dihydrochloride), a novel anti-ischaemic compound, were evaluated in various animal models. In acute pain models, namely acetic acid-induced writhing, hot-plate assay, tail electric stimulation test, capsaicin-induced pain and the formalin test, trimetazidine (1.8-7.2 mg/kg, i.p.) showed marked antinociceptive effects. Trimetazidine did not produce any behavioural impairment as revealed by the mouse rotarod. The inhibition of writhing response by trimetazidine was reduced by yohimbine, theophylline (and to a certain extent by sulpiride) but not by prazosin, guanethidine, naloxone, atropine, propranolol, haloperidol, domperidone, clozapine, glibenclamide or caffeine. The carrageenan-evoked acute paw oedema was reduced by 19.2-21.2 and 17-18.6% by 3.6 and 7.2 mg/kg trimetazidine, respectively. The drug did not alter the oedema-suppressive effect of indomethacin or dexamethasone, but reduced that of rofecoxib. Trimetazidine at 7.2 mg/kg reduced immobility time in Porsolt's forced-swimming test by 28.9%. The acute gastric mucosal lesions evoked by indomethacin in the rat were inhibited in a dose-dependent manner by co-administration of trimetazidine. In anesthetized rats, trimetazidine potentiated the gastric acid secretory response. This study indicates that trimetazidine possesses antinociceptive and gastric protective properties. The antinociceptive properties of trimetazidine are likely to be centrally mediated, but do not involve opioid pathways.
Abdel-Salam
Omar M E
OM
Department of Pharmacology, National Research Centre, Cairo, Egypt. omasalam@hotmail.com
El-Batran
Siham
S
D000208:Acute Disease; D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005744:Gastric Acid / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014292:Trimetazidine / Q000009:adverse effects / Q000494:pharmacology*
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014292:Trimetazidine; D007213:Indomethacin