Abstract: Disubstituted guanidines, e.g., N,N'-di-m-tolyl guanidine, N,N'-di-o-ethylphenyl guanidine, N,N'-di-m-ethylphenyl guanidine, and N,N'-di-o-iodophenyl-guanidine, exhibit a high binding affinity to phenylcyclidine (PCP) receptors. These guanidine derivatives act as non-competitive blockers to glutamate induced responses of the NMDA receptor by acting as blockers for the ion channel of the NMDA receptor-ion channel complex. These compounds thus exert a neuroprotective property and are useful in the therapeautic treatment of neuronal loss in ischemia, hypoxia, hypoglycemia, and brain and spinal cord trauma as well as being useful for the treatment of epilepsy, Alzheimer's disease, Amyotrophic Lateral Sclerosis, Huntington's disease, Down's Syndrome and other neurodegenerative disorders.

Abstract: 1,3-Disubstituted-guanidines, e.g., of the formula ##STR1## wherein R and R' are hydrocarbon groups which preferably are the same, e.g., 1,3-dibutyl-guanidine, 1,3-diphenyl-guanidine and 1,3-di-o-tolyl-guanidine, are highly selective ligands for sigma brain receptors and are useful in the diagnosis and treatment of hallucination associated psychotic mental illness and chronic mental depression. Tritium labeled 1,3-di-(o-tolyl)-guanidine is useful as a screening tool for compounds having selective sigma receptor binding activity, as it is displaced from isolated mammalian brain membrane to which it is bound portionately to the activity of such a compound.