TY - JOUR
T1 - Dopamine enhancement of dextrorphan-induced skin antinociception in response to needle pinpricks in rats
AU - Li, Yu Yu
AU - Chiu, Chong Chi
AU - Wang, Jhi Joung
AU - Chen, Yu Wen
AU - Hung, Ching Hsia
N1 - Funding Information:
The financial support provided by (a) the grant ( MOST 106-2314-B-384-003 ) from the Ministry of Science and Technology, Taiwan and (b) the grant ( CMU107-S-21 ) from the China Medical University, Taiwan .
Funding Information:
The financial support provided by (a) the grant (MOST 106-2314-B-384-003) from the Ministry of Science and Technology, Taiwan and (b) the grant (CMU107-S-21) from the China Medical University, Taiwan.
Publisher Copyright:
© 2019 Institute of Pharmacology, Polish Academy of Sciences
PY - 2019/8
Y1 - 2019/8
N2 - Background: Dextrorphan with long-acting local anesthetic effects did not cause system toxicity as fast as bupivacaine, while catecholamines (i.e., epinephrine) with the vasoconstrictive characteristics enhanced the effects of local anesthetic drugs. The objective of the experiment was to examine the synergistic effect of local dopamine (a catecholamine) injection on cutaneous antinociception of dextrorphan. Methods: The panniculus reflex in response to skin stimulation with a needle was used as the primary endpoint when dextrorphan (1.50, 2.61, 5.46, 10.20 and 20.40 μmol) alone, dopamine (16.20, 32.40, 51.60, 60.00 and 81.60 μmol) alone, or dopamine + dextrorphan (a ratio of ED50 vs. ED50) was injected subcutaneously on the rat's back. We used an isobolographic modelling approach to determine whether a synergistic effect would be observed. Results: We showed that dextrorphan, dopamine, or the mixture of dopamine and dextrorphan produced dose-related skin antinociception. The potency (ED50, 50% effective dose) for cutaneous antinociception was dextrorphan [6.02 (5.93–6.14) μmol] greater than dopamine [48.91 (48.80–49.06) μmol] (p < 0.01). The duration of nociceptive inhibition induced by dopamine was longer than that induced by dextrorphan (p < 0.01) based on their equipotent doses (ED25, ED50, and ED75). Enhancement and prolongation of skin antinociception occurred after co-administration of dopamine with dextrorphan. Conclusions: When compared to dopamine, dextrorphan was more potent and had a shorter duration of skin nociceptive block. Dopamine produced a synergistic effect on dextrorphan-mediated antinociception, and prolonged dextrorphan′s antinociceptive duration.
AB - Background: Dextrorphan with long-acting local anesthetic effects did not cause system toxicity as fast as bupivacaine, while catecholamines (i.e., epinephrine) with the vasoconstrictive characteristics enhanced the effects of local anesthetic drugs. The objective of the experiment was to examine the synergistic effect of local dopamine (a catecholamine) injection on cutaneous antinociception of dextrorphan. Methods: The panniculus reflex in response to skin stimulation with a needle was used as the primary endpoint when dextrorphan (1.50, 2.61, 5.46, 10.20 and 20.40 μmol) alone, dopamine (16.20, 32.40, 51.60, 60.00 and 81.60 μmol) alone, or dopamine + dextrorphan (a ratio of ED50 vs. ED50) was injected subcutaneously on the rat's back. We used an isobolographic modelling approach to determine whether a synergistic effect would be observed. Results: We showed that dextrorphan, dopamine, or the mixture of dopamine and dextrorphan produced dose-related skin antinociception. The potency (ED50, 50% effective dose) for cutaneous antinociception was dextrorphan [6.02 (5.93–6.14) μmol] greater than dopamine [48.91 (48.80–49.06) μmol] (p < 0.01). The duration of nociceptive inhibition induced by dopamine was longer than that induced by dextrorphan (p < 0.01) based on their equipotent doses (ED25, ED50, and ED75). Enhancement and prolongation of skin antinociception occurred after co-administration of dopamine with dextrorphan. Conclusions: When compared to dopamine, dextrorphan was more potent and had a shorter duration of skin nociceptive block. Dopamine produced a synergistic effect on dextrorphan-mediated antinociception, and prolonged dextrorphan′s antinociceptive duration.
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U2 - 10.1016/j.pharep.2019.04.002
DO - 10.1016/j.pharep.2019.04.002
M3 - Article
C2 - 31207435
AN - SCOPUS:85067064453
SN - 1734-1140
VL - 71
SP - 732
EP - 737
JO - Pharmacological Reports
JF - Pharmacological Reports
IS - 4
ER -