Combination of adrenergic agonist and nmda antagonist for relieving chronic painwithout adverse side effects

摘要

A combination of two drugs, from different and unrelated categories, provides effective and long-lasting relief from neuropathic pain and other chronic or intractable pain. Both drugs can be taken in a painless non-invasive manner, such as by means of pills or skin patches. One drug is an alpha 2 adrenergic agonist, exemplified by clonidine. These agents reduce blood pressure and have sedative-hypnotic effects; those are unwanted side effects in a chronic daily treatment for pain. The other drug is an NMDA antagonist which can be described as mild, minimally toxic, and/or inherently safe (or safened). Three such classes of drugs have been shown to work exceptionally well, with clonidine, in reducing neuropathic pain for prolonged periods: (1) aryl-cyclo-alkanolamine drugs such as procyclidine and biperiden; (2) tricyclo-alkylamine drugs such as ethopropazine; and (3) adamantane derivatives such as memantine. None of these drugs, by itself, can provide effective relief for neuropathic pain; at doses required to provide short-term relief, they cause adverse side effects, and any pain relief they provide is relatively brief. However, when combined with an alpha 2 adrenergic agonist, the two drugs potentiate one another's pain-relieving action, and provide potent and sustained relief, even when each drug is administered at a low dosage that is below its threshold for causing adverse side effects.