Adenosine A.sub.1 receptor antisense oligonucleotide treatment o

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

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435 6, 435 91, 435325, 435354, 435375, 536 231, 536 243, 536 2431, 536 245, A61K 4800, C07H 2104, C12Q 168, C12N 1585

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active

059325577

ABSTRACT:
Preclinical studies in mice and rats based on three microinfusions (12 hours apart) of specifically designed and synthesized adenosine A.sub.1 receptor antisense oligonucleotide with the sequence: (A.sub.1 Antisense: 5'-GGCCGAGATGGAGGGCGGCAT-3' (SEQ ID NO: 1)) and as a control, a mismatched antisense nucleotide with a sequence: (A.sub.1 Sense: 5'-ATGCCGCCCTCCATCTCGGCC-3' (SEQ ID NO: 1)) established that the "functional knock out" of A.sub.1 receptors protected the animals from the well known motor incoordination due to alcohol or .DELTA..sup.9 -tetrahydrocarnabinol(THC: the major psychoactive component of marijuana intake). The motor coordination in animals was evaluated by the mouse/rat rotorod treadmill. The antisense was microinfused in mouse cerebellum and in the rat motor cortex whereas ethanol was always administered systemically. However, unlike ethanol, the .DELTA..sup.9 -THC was microinfused into the mouse cerebellum following the cerebellar pretreatment with the antisense. In addition to protection of alcohol or the .DELTA..sup.9 -THC-induced motor incoordination the above antisense molecule should block all functions expressed via adenosine A.sub.1 receptor, such as hypnosis and general CNS intoxication, thereby, further expanding the clinical applications of this oligonucleotide. This antisense may also be useful in treating asthma and anginal chest pains.

REFERENCES:
patent: 5320962 (1994-06-01), Stiles et al.
Rojanasakul, Antisense Oligonucleotide Therapeutics: Drug Delivery and Targeting, Advanced Drug Delivery Reviews 18, 115-131 (1996).
Gewirtz, Facilitating Oligonucleotide Delivery: Helping Antisense Deliver on its Promise, PNAS 93, 3161-3163 (1996).

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