Effects of an intrathecally administered benzodiazepine receptor agonist, antagonist and inverse agonist on morphine-induced inhibition of a spinal nociceptive reflex.

Abstract:

:1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none of these compounds significantly altered pain threshold. 3. The BZR agonist midazolam enhanced the morphine-induced antinociceptive effect whereas the antagonist flumazenil did not alter it. In contrast, the BZR inverse agonist Ro 19-4603 decreased the morphine-induced antinociceptive effect. 4. Naloxone (1 mg kg-1 i.p.) completely reversed all these effects. 5. These results demonstrate that BZR agonists and inverse agonists are able to affect, by allosteric up- or down-modulation of gamma-aminobutyric acidA (GABAA)-receptors, the transmission of nociceptive information at the spinal cord level, when this transmission is depressed by mu-opioid receptor activation.

journal_name

Br J Pharmacol

authors

Moreau JL,Pieri L

doi

10.1111/j.1476-5381.1988.tb11486.x

subject

Has Abstract

pub_date

1988-04-01 00:00:00

pages

964-8

issue

4

eissn

0007-1188

issn

1476-5381

journal_volume

93

pub_type

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