Does nitric oxide participate in the mechanism of action of dotarizine?
Behavioral and nociceptive effects of dotarizine (DOT) and other substances acting on migrainous attacks and nitric oxide (NO) metabolism were studied in comparative experiments on rats. Behavioral effects were evaluated by the changes induced in ambulations and rearings of rats in the Opto-Varimex apparatus; effects on nociception were determined by the changes of pain threshold in growing mechanical pressure on one of the rat paw. The data showed that (1) NO did not participate directly in the mechanism of the behavioral actions of DOT. A role could be ascribed to the modulating influence of DOT on the changes in NO formation induced by other agents; (2) the NO system did not participate in the mechanisms of the responses to the painful mechanical pressure on the rat paw; (3) the behavioral effects of the substances with facilitating or inhibitory action on the migrainous process (m-CPP and ergotamine) and the influence of substances proved to affect NO formation (L-arginine, histamine, L-NAME) on these effects suggest a role for NO as a modulating but not a basic factor in the mechanisms of action of these pro- and antimigrainous substances; and (4) the behavioral effects of DOT were similar to the effects of the antimigrainous drug ergotamine and different from the promigrainous drug meta-chlorophenyl-piperazine (m-CPP)--which suggest an antimigrainous activity of dotarizine.
Petkov
V D
VD
Institute of Physiology, Bulgarian Academy of Sciences.
Belcheva
S
S
Konstantinova
E
E
Petkov
V V
VV
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004878:Ergotamine / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D001559:Benzhydryl Compounds; D002121:Calcium Channel Blockers; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D014665:Vasodilator Agents; D009569:Nitric Oxide; D006632:Histamine; D001120:Arginine; C083946:dotarizine; D004878:Ergotamine; D005444:Flunarizine; C015068:1-(3-chlorophenyl)piperazine; D019331:NG-Nitroarginine Methyl Ester