Intra-periaqueductal grey microinjections of an imidazo[1,2-b]pyridazine derivative, DM2, affects rostral ventromedial medulla cell activity and shows antinociceptive effect

Neuropharmacology
Enza PalazzoSabatino Maione

Abstract

The 6-methoxy-2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acid, DM2, exerts anti-absence activity and blocks Cav3.1 channel, a T-type voltage-dependent Ca(2+) channel subtype, in vitro. The current study investigated the effect of intra-ventrolateral periaqueductal grey (VLPAG) administration of DM2 on formalin-induced nocifensive responses in rats. In addition, the effect of intra-VLPAG microinjection of DM2 on the ongoing and tail flick-related activities of rostral ventromedial medulla (RVM) cell population was also investigated. Formalin was injected subcutaneously into the dorsal surface of the hind paws of awake rats. We found that DM2 reduced nocifensive responses in the late phase of the formalin test. Moreover, in the RVM, the intra-VLPAG microinjection of DM2 reduced the ongoing and tail flick-related activity of the nociceptive ON cells, whereas it increased the ongoing activity and reduced the tail flick-induced pause of the antinociceptive OFF cells, consistent with antinociception. Behavioural and electrophysiological effects were reproduced by intra-VLPAG microinjection of ethosuximide, a conventional T-type Ca(2+) channel blocker. Finally, DM2 administration did not produce any adverse cardiovascular effects a...Continue Reading

References

May 4, 1977·Proceedings of the Royal Society of London. Series B, Containing Papers of a Biological Character·D Mitchell, R F Hellon
Oct 1, 1992·Pain·A TjølsenK Hole
Jun 21, 1988·Brain Research·F P Zemlan, M M Behbehani
Sep 1, 1989·Pain·Manabu ShibataReizo Inoki
Feb 19, 1985·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·H L Fields, M M Heinricher
Oct 1, 1986·Physiology & Behavior·J P Kroon, A L Riley
Jan 1, 1994·Brain Research Bulletin·Q P Wang, Y Nakai
Jun 1, 1994·Trends in Pharmacological Sciences·A DrayA Dickenson
Jan 1, 1994·Annals of Neurology·H Fields
Nov 3, 2001·Naunyn-Schmiedeberg's Archives of Pharmacology·L BerrinoS Maione
May 21, 2004·Journal of Neurophysiology·Mary M Heinricher, Miranda J Neubert
Jul 28, 2004·Pain·Miranda J NeubertMary M Heinricher
Dec 20, 2005·European Journal of Pharmacology·Patrizia OlivaSabatino Maione
Aug 31, 2006·Genes, Brain, and Behavior·S ChoiH-S Shin
Dec 16, 2006·CNS & Neurological Disorders Drug Targets·Slobodan M Todorovic, Vesna Jevtovic-Todorovic
Aug 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Marcello TrevisaniPierangelo Geppetti

❮ Previous
Next ❯

Citations

Jan 13, 2012·The Journal of Comparative Neurology·Charles P SevignyAndrew M Allen

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.