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Abstract

Characterization of the pharmacology of intrathecally administered alpha-2 agonists and antagonists in rats.

Y Takano and T L Yaksh
Journal of Pharmacology and Experimental Therapeutics May 1992, 261 (2) 764-772;
Y Takano
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T L Yaksh
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Abstract

To examine the pharmacology of the spinal alpha receptor which modulates nociceptive transmission, the antinociceptive effects (52.5 degrees C hot plate; HP) of three i.t. administered alpha-2-preferring agonists [dexmedetomidine (DMET); clonidine (CLON) and ST-91] were determined. The antagonist potency of atipamezole (ATI), idazoxan (IDAZ), yohimbine (YOH) and prazosin (PRA), adrenergic antagonists with differing alpha-2-preferring profiles, were then examined for each of the three agonists. The three agonists produced a dose-dependent block of the HP response with the ED50 and the dose which was just maximally effective being DMET (3.2 and 10 micrograms); CLON (27 and 100 micrograms) and ST-91 (6.1 and 20 micrograms). After determining the time of peak antagonist effect, studies were run in which the just maximally effective dose of each agonist was given in conjunction with one of several doses of the several antagonists. The rank order of potency (and ID50 in microgram) for the several antagonists against each of the three agonists was: DMET = [IDAZ (1.9); ATI (4.1); YOH (70); PRA (greater than 100)]; CLON = [ATI (2.7); IDAZ (23); YOH (52); PRA (greater than 100)]; ST-91 = [PRA (38); YOH (69); ATI (greater than 100); IDAZ (greater than 100)]; where antagonists joined by a common line display overlapping 95% confidence intervals and greater than (greater than) indicates failure to achieve a 50% reversal at the highest antagonist dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 261, Issue 2
1 May 1992
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Abstract

Characterization of the pharmacology of intrathecally administered alpha-2 agonists and antagonists in rats.

Y Takano and T L Yaksh
Journal of Pharmacology and Experimental Therapeutics May 1, 1992, 261 (2) 764-772;

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Abstract

Characterization of the pharmacology of intrathecally administered alpha-2 agonists and antagonists in rats.

Y Takano and T L Yaksh
Journal of Pharmacology and Experimental Therapeutics May 1, 1992, 261 (2) 764-772;
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