Abstract | BACKGROUND: METHODS: RESULTS: The median maximally tolerated dose was 1.3 +/- 0.4 (range, 0.9-2.0) mg/kg. Tests of cognitive and neurological function were unchanged. Dose-limiting side effects were hazy vision in 95% of volunteers and sedation in 40%. There were no significant changes in electrical or warm-cool detection and pain thresholds or heat pain thresholds. LY293558 had little effect on brief pain sensations in normal skin. Both high and low doses of LY293558 significantly reduced pain intensity, pain unpleasantness, and the area in which light brush evoked pain after intradermal capsaicin. There was a trend toward a dose-response effect of LY293558 on the area in which pinprick evoked pain after intradermal capsaicin, which did not reach statistical significance. CONCLUSIONS: The authors infer that AMPA-KA receptor blockade reduces the spinal neuron sensitization that mediates capsaicin-evoked pain and allodynia. The low incidence of side effects at effective doses of LY293558 suggests that this class of drugs may prove to be useful in clinical pain states.
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Authors | C N Sang, M P Hostetter, R H Gracely, A S Chappell, D D Schoepp, G Lee, S Whitcup, R Caruso, M B Max |
Journal | Anesthesiology
(Anesthesiology)
Vol. 89
Issue 5
Pg. 1060-7
(Nov 1998)
ISSN: 0003-3022 [Print] United States |
PMID | 9821993
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Analgesics, Non-Narcotic
- Isoquinolines
- Receptors, AMPA
- Receptors, Kainic Acid
- Tetrazoles
- tezampanel
- Capsaicin
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Topics |
- Adult
- Analgesics, Non-Narcotic
(pharmacology)
- Capsaicin
- Dose-Response Relationship, Drug
- Hot Temperature
- Humans
- Hyperalgesia
(chemically induced, drug therapy)
- Isoquinolines
(pharmacology)
- Male
- Middle Aged
- Nociceptors
(drug effects)
- Pain
(chemically induced, drug therapy)
- Pain Measurement
(drug effects)
- Pain Threshold
(drug effects)
- Physical Stimulation
- Receptors, AMPA
(antagonists & inhibitors)
- Receptors, Kainic Acid
(antagonists & inhibitors)
- Skin
(drug effects)
- Tetrazoles
(pharmacology)
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