Abstract
Both the γ-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[1-piperazinyl]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
| Original language | English |
|---|---|
| Pages (from-to) | 179-184 |
| Number of pages | 6 |
| Journal | European Journal of Pharmacology |
| Volume | 90 |
| Issue number | 2-3 |
| DOIs | |
| State | Published - Jun 3 1983 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Cellular and Molecular Neuroscience
- Pharmacology
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A comparison of the analgesic activities of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and 6-chloro-2[1-piperazinyl]pyrazine (MK 212). / Murray, Thomas F.; McGill, William; Cheney, Darwin L.
In: European Journal of Pharmacology, Vol. 90, No. 2-3, 03.06.1983, p. 179-184.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A comparison of the analgesic activities of 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and 6-chloro-2[1-piperazinyl]pyrazine (MK 212)
AU - Murray, Thomas F.
AU - McGill, William
AU - Cheney, Darwin L.
PY - 1983/6/3
Y1 - 1983/6/3
N2 - Both the γ-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[1-piperazinyl]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
AB - Both the γ-aminobutyric acid (GABA) mimetic, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol and the serotonergic agonist, MK 212 (6-chloro-2[1-piperazinyl]pyrazine) are effective analgesic agents in the mouse hot plate assay. Naltrexone, however, fails to reverse the analgesia elicited by either compound. Acute injection of THIP potentiates the morphine analgesia and chronic administration of THIP produces a functional tolerance to its analgesic effects. MK 212 antagonizes the analgesia induced by either morphine or THIP. These results support the postulate that GABAergic and serotonergic synapses represent two synaptic mechanisms which participate in the modulation of pain threshold in a manner that is independent from opioid receptors. Moreover, GABA and serotonin appear to be able to modulate opioid-mediated analgesia in an opposing manner with GABAergic mechanisms facilitating and serotonergic mechanisms inhibiting morphine-induced antinociception.
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U2 - 10.1016/0014-2999(83)90235-2
DO - 10.1016/0014-2999(83)90235-2
M3 - Article
VL - 90
SP - 179
EP - 184
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -