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

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.