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ω-Agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism

Involvement of P-type voltage-dependent Ca 2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-agatoxin IVA (25 ng) intrathec...

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Published in:European journal of pharmacology 1996-10, Vol.314 (3), p.293-300
Main Authors: Roerig, Sandra C., Howse, Kurt M.
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Language:English
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description Involvement of P-type voltage-dependent Ca 2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca 2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.
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Pharmacogenetics. Drug-receptor interactions</topic><topic>Pharmacology. Drug treatments</topic><topic>Spider Venoms - pharmacology</topic><topic>Spinal Cord - drug effects</topic><topic>Substance-Related Disorders - prevention &amp; control</topic><topic>Tolerance</topic><topic>Virulence Factors, Bordetella - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Roerig, Sandra C.</creatorcontrib><creatorcontrib>Howse, Kurt M.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium &amp; Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><jtitle>European journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Roerig, Sandra C.</au><au>Howse, Kurt M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>ω-Agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism</atitle><jtitle>European journal of pharmacology</jtitle><addtitle>Eur J Pharmacol</addtitle><date>1996-10-31</date><risdate>1996</risdate><volume>314</volume><issue>3</issue><spage>293</spage><epage>300</epage><pages>293-300</pages><issn>0014-2999</issn><eissn>1879-0712</eissn><coden>EJPHAZ</coden><abstract>Involvement of P-type voltage-dependent Ca 2+ channels in spinal morphine- or clonidine-induced antinociception and in the synergistic interaction between morphine and clonidine was examined in the present studies. Coadministration of the selective P-type antagonist, ω-agatoxin IVA (25 ng) intrathecally (i.t.) to mice along with morphine or clonidine enhanced the tail flick antinociception of each agonist 5–6-fold. The greater-than-additive (synergistic) interaction that occurred when morphine and clonidine were coadministered i.t. decreased to an additive interaction in the presence of ω-agatoxin IVA. In mice pretreated with pertussis toxin (10 ng) to inactivate G proteins, ω-agatoxin IVA did not alter the morphine/clonidine synergism. Surprisingly, ω-agatoxin IVA reversed the additive morphine/clonidine interaction that occurs in morphine-tolerant mice back to synergism. These results suggest that functional P-type Ca 2+ channels play an essential role in the antinociceptive synergism between spinal morphine and clonidine.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>8957249</pmid><doi>10.1016/S0014-2999(96)00561-4</doi><tpages>8</tpages></addata></record>
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subjects Analgesics, Opioid - antagonists & inhibitors
Animals
Antinociception, spinal
Biological and medical sciences
Ca 2+ channel, P-type
Calcium Channel Blockers - pharmacology
Clonidine
Clonidine - antagonists & inhibitors
Drug Synergism
Drug Tolerance
G-protein
General pharmacology
Linear Models
Male
Medical sciences
Mice
Mice, Inbred ICR
Morphine
Morphine - antagonists & inhibitors
Morphine Dependence - prevention & control
omega-Agatoxin IVA
Pertussis Toxin
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Spider Venoms - pharmacology
Spinal Cord - drug effects
Substance-Related Disorders - prevention & control
Tolerance
Virulence Factors, Bordetella - pharmacology
title ω-Agatoxin IVA blocks spinal morphine/clonidine antinociceptive synergism
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