Abstract: Disclosed are methods of neuroprotection or treatment of neurodegenerative disorders with Ras antagonists.

Abstract: Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Abstract: Disclosed is a method for inhibiting Ras-induced or mediated proliferation of cells associated with a non-malignant disease, disorder or pathological condition. The method entails administering to a patient a Ras antagonist in an amount effective to inhibit the proliferation. The invention is particularly applicable to diseases characterized by a proliferation of T-cells such as autoimmune disease, e.g., type 1 diabetes, lupus and multiple sclerosis, and pathological states such as graft rejection induced by the presentation of a foreign antigen such as a graft in response to a disease condition (e.g., kidney failure). Other non-malignant diseases characterized by proliferations of cells include cirrhosis of the liver and restenosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Abstract: Disclosed is the identity of various Ras cell membrane anchor proteins. Also disclosed are methods for identifying other anchor proteins that bind isoforms of Ras, methods of identifying drug candidates that inhibit aberrant Ras activity and methods of determining therapeutic dosages of the drugs. Further disclosed are methods for disrupting aberrant Ras activity in vivo.

Abstract: Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Abstract: A drug screening assay for identifying compounds for their potential effects on the long chain fatty acid dependant intracellular membrane anchorage sites of lipoproteins. Membranes-anchoring-target are incubated in the presence of the compound to be tested and the proportion of the target that is released by the compound is detected and quantitated. The benchmark for this assay are the prenylated proteins such as the farnesylated and palmitoylated oncogenic ras trigger proteins which are displaced from their anchorage at the intracellular plasma membrane by derivatives of Farnesyl Thiosalicylic Acid (FTS). The assay is adaptable to flexibly assay a large variety of anchored targets using a wide range of labeling and detection techniques in test wells, tissue culture, and in animals as injected cells or transgenic, thereby directly addressing a wide range of pharmacologically relevant needs.

Abstract: Disclosed is a method for inhibiting Ras-induced or mediated proliferation of cells associated with a non-malignant disease, disorder or pathological condition. The method entails administering to a patient a Ras antagonist in an amount effective to inhibit the proliferation. The invention is particularly applicable to diseases characterized by a proliferation of T-cells such as autoimmune disease, e.g., type 1 diabetes, lupus and multiple sclerosis, and pathological states such as graft rejection induced by the presentation of a foreign antigen such as a graft in response to a disease condition (e.g., kidney failure). Other non-malignant diseases characterized by proliferations of cells include cirrhosis of the liver and restenosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Abstract: Disclosed are methods for inhibiting Ras activity such as cell proliferation associated with vascular injury such as post-angioplasty restenosis and atherosclerosis. Preferred Ras antagonists are S-trans-trans farnesylthiosalicylic acid (FTS) and structurally related compounds (or analogs) thereof.

Abstract: The present invention relates to pharmaceutical compositions for preventing or alleviating neurotoxicity. Said pharmaceutical compositions comprise as their active ingredient the stereospecific (+) enantiomers, having (3S,4S) configuration, of .DELTA..sup.6 -tetrahydrocannabinol (THC) type compounds of general formula (I), as defined hereinbelow.

Abstract: Novel farnesyl derivatives which are inhibitors of the prenylated protein thyltransferase enzyme, and useful as anti-cancer drugs, have the following formula: ##STR1## wherein R.sup.1 represents farnesyl, geranyl or geranyl-geranyl;Z represents C--R.sup.6 or N;R.sup.2 represents H, CN, the groups COOR.sup.7, SO.sub.3 R.sup.7, CONR.sup.7 R.sup.8 and SO.sub.2 NR.sup.7 R.sup.7, wherein R.sup.7 and R.sup.8 are each independently hydrogen, alkyl, alkenyl, and the groups COOM and SO.sub.3 M, wherein M is a cation;R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are each independently hydrogen, carboxyl, alkyl, alkenyl, aminoalkyl, nitroalkyl, nitro, halo, amino, mono- or di-alkylamino, mercapto, mercaptoalkyl, azido, or thiocyanato;X represents O, S, SO, SO.sub.2, NH or Se; and the quaternary ammonium salts and N-oxides of the compounds of formula I wherein Z is N.

Abstract: Pharmaceutical compositions are described for preventing neurotoxicity, crising as active ingredient the stereospecific (+) enantiomer, having (3S,4S) configuration of .DELTA..sup.6 tetrahydrocannabinol type compounds. The compositions are particularly effective in alleviating and even preventing neurotoxicity due to acute injuries to the central nervous system, including mechanical trauma, compromised or reduced blood supply as may occur in cardiac arrest or stroke, or poisonings. They are also effective in the treatment of certain chronic degenerative diseases characterized by gradual neuronal loss.

Abstract: The use of a compound of the formula: ##STR1## having the (3S,4S) configuration, and which is essentially free of the (3R,4R) enantiomer, wherein A--B designates a 1(2) or a 6(1) double bond, R designates --CH.sub.3 or --CH.sub.2 OH, R.sup.1 designates a hydrogen atom or a lower acyl group, and R.sup.2 designates (A) a straight-chained or branched C.sub.6-12 alkyl radical; or (B) a group --O--R.sup.3, in which R.sup.3 is a straight-chained or branched C.sub.5-9 alkyl radical or a straight-chained or branched alkyl radical substituted at the terminal carbon atom by a phenyl group in the manufacture of a medicament for reducing or preventing glutamate neurotoxicity. Some of the above compounds are novel, and their preparation is described.

Abstract: The invention relates to a drug system for the treatment and alleviation of the symptoms of epilepsy; as anticonvulsant agent, and for the prevention or alleviation of brain damage due to strokes. The drug system comprises as active ingredient a compound such as MK-801, phencyclidine or as thienyl-cyclohexyl-piperidine (TCP), which is administered in such a manner that it encounters and binds to the N-methyl-D-aspartate (NMDA) receptor channels. This is in the presence of glutamate or glycine, or similarly acting amino-acid, which is either present in the patient, or which can be administered separately. The effective drug can be effectively locked in the receptor channels by means of a glutamate antagonist, such as AP-5.

Abstract: Novel farnesyl derivatives which are inhibitors of the prenylated protein methyltransferase enzyme, and useful as anti-cancer drugs, have the following formula: wherein R1represents farnesyl, geranyl or geranyl-geranyl; Z represents C—R6 or N; R2 represents H, CN, the groups COOR7, SO3R7, CONR7R8 and SO2NR7R7, wherein R7 and R8 are each independently hydrogen, alkyl, alkenyl, and the groups COOM and SO3M, wherein M is a cation; R3, R4, R5 and R6 are each independently hydrogen, carboxyl, alkyl, alkenyl, aminoalkyl, nitroalkyl, nitro, halo, amino, mono- or di-alkylamino, mercapto, mercaptoalkyl, azido, or thiocyanato; X represents O, S, SO, SO2, NH or Se; and the quaternary ammonium salts and N-oxides of the compounds of formula I wherein Z is N.