Antinociceptive action of (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid in mice.
The objective of this study was to investigate spinal and supraspinal antinociceptive effects of a new synthetic compound, (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid (tetrahydropyran derivative). Its activity was compared with those from morphine. In peripheral models of inflammation and hyperalgesia, tetrahydropyran derivative significantly reduced nociceptive effect induced by acetic acid or formalin in mice. Tetrahydropyran derivative developed antinociceptive effect on the tail-flick and hot-plate tests with a long-acting curve maintaining the effect for 4 h longer than morphine. The opioid receptor antagonist naloxone totally reverted tetrahydropyran derivative effects on both models. Morphine as well as tetrahydropyran derivative induced tolerance and sedation in mice. However, tetrahydropyran derivative-induced tolerance had its onset retarded and the sedative activity was lower when compared to that induced by morphine. These results indicate that this new substance develops an antinociceptive activity and may be used in the future as a substitute for traditional opioids.
Marinho
Bruno G
BG
Departamento de Farmacologia Básica e Clínica/ICB, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Cidade Universitária, Caixa Postal 68016, 21944-970, Rio de Janeiro, Brazil.
Miranda
Leandro S M
LS
Gomes
Niele M
NM
Matheus
Maria Eline
ME
Leitão
Suzana G
SG
Vasconcellos
Mario Luiz A A
ML
Fernandes
Patrícia D
PD
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005557:Formaldehyde; D005561:Formates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D006358:Hot Temperature; D008297:Male; D051379:Mice; D009043:Motor Activity; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D011714:Pyrans / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects; D013131:Spine / Q000187:drug effects
D000700:Analgesics; D005561:Formates; D009292:Narcotic Antagonists; D011714:Pyrans; D011957:Receptors, Opioid; C515488:cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid; D005557:Formaldehyde; D009270:Naloxone; D019342:Acetic Acid