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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Bibliographic Details
Published in:European journal of pharmacology 1996-10, Vol.314 (3), p.293-300
Main Authors: Roerig, Sandra C., Howse, Kurt M.
Format: Article
Language:English
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
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Summary: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.
ISSN:0014-2999
1879-0712
DOI:10.1016/S0014-2999(96)00561-4