L-type and T-type calcium channel blockade potentiate the analgesic effects of morphine and selective mu opioid agonist, but not to selective delta and kappa agonist at the level of the spinal cord in mice.
We examined the effects of amlodipine, a selective L-type voltage dependent Ca(2+) channel (VDCC) blocker, and mibefradil, a selective T-type VDCC blocker on the antinociceptive effects of morphine, and mu, delta and kappa opioid receptor selective agonist-induced antinociception at the spinal level. Intrathecally administered amlodipine and mibefradil potentiated morphine and [D-Ala(2), N mePhe(4), Gly-ol(5)] enkephalin (DAMGO)-induced antinociception by shifting their dose response curves to the left. However, intrathecally administered amlodipine and mibefradil did not affect [D-Pen(2), D-Pen(5)]enkephalin (DPDPE) and [trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrolidinyl)cyclohexyl] benzene acetamide (U-50, 488H)-induced antinociception. These data indicate that L-type and T-type VDCC blockers synergistically potentiate the analgesic effects of mu opioid receptor agonists, but not delta and kappa opioid receptor agonists, at the spinal level. Additionally, these data suggest that there is an important functional interaction between L-type and/ or T-type VDCC and mu opioid receptors in the process of analgesia.
Doğrul
Ahmet
A
Department of Medical Pharmacology, Faculty of Medicine, Gülhane Military Academy of Medicine, Ankara, Turkey Department of Anesthesiology, Faculty of Medicine, Gülhane Military Academy of Medicine, Ankara, Turkey.
Yeşilyurt
Özgür
Ö
Işmer
Aşkn
A
Güzeldemir
Erdal M
EM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D017311:Amlodipine / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D020747:Calcium Channels, T-Type / Q000187:drug effects*; D004357:Drug Synergism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D008297:Male; D020748:Mibefradil / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D013116:Spinal Cord / Q000187:drug effects*
D000701:Analgesics, Opioid; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020747:Calcium Channels, T-Type; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D017311:Amlodipine; D020748:Mibefradil; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-