Combination of adrenergic agonist and tricyclo-alkylamine for relieving chronic pain without adverse side effects

摘要

This invention discloses that a combination of two drugs, from two different and previously unrelated categories, provides effective and long-lasting relief from neuropathic pain. Both drugs can be taken orally, in a convenient, painless, non-invasive manner that does not require injections. One drug in this combination is an &agr;2 adrenergic agonist, exemplified by clonidine. The other drug in the pain-relieving combination has a tri-cyclo-alkyl-amine (TCAA) structure. At least some TCAA drugs have antagonist (receptor-blocking) activity at two entirely different classes of neuronal receptors: the muscarinic subclass of acetylcholine (ACh) receptors, and the NMDA subclass of glutamate receptors. Such drugs include ethopropazine, normally used as an anti-cholinergic drug, and desipramine, normally used as an anti-depressant. Tests by the Applicants have shown that at least some TCAA drugs can relieve neuropathic pain to a limited extent, but at the doses required to relieve pain, they cause adverse side effects, and any pain relief is relatively brief and short-lived. However, when a TCAA drug such as ethopropazine is administered together with an &agr;2 adrenergic agonist such as clonidine, these drugs mutually potentiate one another's neuropathic pain-relieving action, and provide potent and sustained neuropathic pain relief, even when each agent is administered at a low dosage that is below its threshold for causing adverse side effects. Accordingly, this drug combination can provide safe and effective relief of neuropathic pain and possibly other types of chronic and/or intractable pain, at dosages which are so low that they do not pose serious risks of adverse side effects.