Antinociceptive activity of impentamine, a histamine congener, after CNS administration

Citation
Lb. Hough et al., Antinociceptive activity of impentamine, a histamine congener, after CNS administration, LIFE SCI, 64(5), 1998, pp. PL79-PL86
Citations number
21
Categorie Soggetti
Biochemistry & Biophysics
Journal title
LIFE SCIENCES
ISSN journal
00243205 → ACNP
Volume
64
Issue
5
Year of publication
1998
Pages
PL79 - PL86
Database
ISI
SICI code
0024-3205(199812)64:5<PL79:AAOIAH>2.0.ZU;2-9
Abstract
The brain neuromodulator histamine induces antinociception when administere d directly into the rodent CNS. However, several compounds derived from H-2 and H-3 antagonists also produce antinociception after central administrat ion. Pharmacological studies have shown that a prototype of these agents, i mprogan, induces analgesia that is not mediated by actions on known histami ne receptors. Presently, the antinociceptive properties of a compound that chemically resembles both improgan and histamine were investigated in rats. Intraventricular (ivt) administration of impentamine (4-imidazolylpentylam ine) induced reversible, near-maximal antinociception on the hot plate and tail flick tests (15 mu g, 98 nmol). The dose-response function was extreme ly steep, however, since other doses showed either no effect or behavioral toxicity. On the tail flick test, impentamine antinociception was resistant to antagonism by blockers of H-1, H-2, or H-3 receptors, similar to charac teristics previously found for improgan. In contrast, histamine antinocicep tion was highly attenuated by H-1 and H-2 antagonists. These findings sugge st that: 1) the histamine congener impentamine may induce antinociception b y a mechanism similar to that produced by improgan, and 2) additional hista mine receptors may be discovered that are linked to pain-attenuating proces ses. (C) 1998 Elsevier Science Inc.