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.