Abstract: 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.

Abstract: This invention discloses that a combination of two drugs, from two different and 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 is an aryl-cyclo-alkanolamine (ACAA) which has antagonist (receptor-blocking) activity at the NMDA subclass of glutamate receptors; such drugs include procyclidine, biperiden, and trihexyphenidyl. The other drug is an &agr;2 adrenergic agonist, exemplified by clonidine. When an ACAA drug which blocks NMDA receptors, such as procyclidine, 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.

Abstract: A method of treating Alzheimer's disease is disclosed, not just with palliatives, but in a manner that prevents the progressive degeneration caused by Alzheimer's disease. Certain types of “safener” drugs, which can reduce the neurotoxic damage caused by a potent NMDA antagonist drug such as dizocilpine maleate (also known as MK-801) can also retard the type of corticolimbic damage which, in the brain of a patient who suffers from Alzheimer's disease, results from over-excitation of corticolimbic neurons. This over-excitation is caused or aggravated by NMDA receptor dysfunction in neuronal circuits which normally limit and control excitatory neurotransmitter release within those corticolimbic regions. Safener drugs include various known drugs that can suppress activity at muscarinic acetylcholine receptors, sigma receptors, kainic acid receptors, or AMPA receptors. They also include various drugs which can stimulate activity at alpha-2 adrenergic or 5HT-2A serotonin receptors.

Abstract: 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 combination is an adamantane derivative which has NMDA antagonist activity, such as memantine. Tests described herein demonstrate that when memantine 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.

Abstract: Methods for treating the very early (presymptomatic) stages of Alzheimer's disease are disclosed, wherein NMDA antagonist drugs are administered to protect NMDA receptors against neuronal damage. Since NMDA antagonists may cause a condition known as NMDA receptor hypofunction (NR/hypo) that triggers neurotoxic side effects, they may be co-administered with, or have inherent activity as, "safener" drugs to prevent toxic side effects. The patient's status must be monitored, so that any NMDA antagonist drugs can be discontinued if a condition of NR/hypo arises. Otherwise, the NMDA antagonist drugs can worsen and accelerate the damage caused by the disease.

Abstract: This invention relates to a new method for treating or preventing brain damage caused by NMDA receptor hypofunction (NR/hypo), using drugs such as lisuride which stimulate (agonize) activity at the 5HT-2A class of serotonin receptors, but which do not cause hallucinations. Data disclosed herein indicate that stimulation of both 5HT-2A and 5HT-2C receptors causes hallucinations, while stimulation of 5HT-2A receptors but not 5HT-2C receptors does not. Accordingly, to be useful herein, non-hallucinatory 5HT-2A agonists should either (1) antagonize (suppress) activity at 5HT-2C receptors, or (2) have no significant effect on activity at 5HT-2C receptors. Selective non-hallucinatory 5HT-2A agonists can be used in either of two treatment methods disclosed herein.One such treatment comprises administering a 5HT-2A receptor agonist as a "safener drug" which accompanies an NMDA antagonist drug that is being used for a therapeutic purpose.

Abstract: A method for reducing progressive neuronal degeneration due to Alzheimer's disease is disclosed wherein a neuroprotective drug selected from the group consisting of clozapine, olanzapine and fluperlapine, and salts, isomers and analogs thereof, is administered.

Abstract: Methods and compositions are disclosed for treating or preventing adverse CNS effects produced by NMDA receptor hypofunction (NRH), including hypofunction induced by NMDA antagonist drugs, and hypofunction occurring as a causative or aggravating factor in schizophrenia. One method of this invention comprises administering an alpha-2 adrenergic (.alpha.2) receptor agonist drug along with an NMDA antagonist drug. The NMDA antagonist drug exerts a primary benefit in reducing excitotoxic brain damage, alleviating neuropathic pain, or preventing or avoiding tolerance or addiction to various types of drugs. The .alpha.2 agonist drug acts as a secondary or "safener" drug, to prevent the neurotoxic side effects that would be caused by the NMDA antagonist in the absence of the safener drug. Another method disclosed herein involves the use of an .alpha.