Abstract The brain neuromodulator histamine induces antinociception when administered directly into the rodent CNS. However, several compounds derived from H 2 and H 3 antagonists also produce antinociception after central administration. Pharmacological studies have shown that a prototype of these agents, improgan, induces analgesia that is not mediated by actions on known histamine 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-imidazolylpentylamine) induced reversible, near-maximal antinociception on the hot plate and tail flick tests (15 μg, 98 nmol). The dose-response function was extremely 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 characteristics previously found for improgan. In contrast, histamine antinociception was highly attenuated by H 1 and H 2 antagonists. These findings suggest that: 1) the histamine congener impentamine may induce antinociception by a mechanism similar to that produced by improgan, and 2) additional histamine receptors may be discovered that are linked to pain-attenuating processes.