BENZOPYRANOPYRIDINES AS NOVEL ANALGESIC AGENTS

IN THIS PROJECT, THE INVESTIGATORS PROPOSE TO PREPARE AND EVALUATE PHARMACOLOGICALLY SIX NITROGEN CONTAINING ANALOGS OF DELTA-9-TETRA-HYDROCANNABINOLS INCLUDING TWO WATER SOLUBLE DERIVATIVES. THESE COMPOUNDS ARE DESIGNED AND M MODELED AFTER THE ACTIVE PRINCIPLE OF CANNABIS SATIVA B BECAUSE THE TETRAHYDROCANNABINOLS ARE UNLIKE OTHER DRUGS ACTING ON THE CENTRAL NERVOUS SYSTEM. NATURAL TETRAHYDROCANNABINOLS ARE UNIQUE BECAUSE (A) THEY CONTAIN NONITROGEN IN THEIR STRUCTURES; (B) THEY ARE NOT LETHAL TO LABORATORY ANIMALS WHEN ADMINISTERED ORALLY; (C) THEY SHOW LITTLE OR NO EFFECT ON RESPIRATION; AND (D) NONE HAVE EVER BEEN REPORTED TO RESULT IN PHYSICAL ADDICTION OR LETHALITY. PRELIMINARY RESULTS HAVE SHOWN PAIN RELIEF WHICH IS SIX TIMES THE POTENCY OF CODEINE IN THE RELIEF OF POST-OPERATIVEPAIN DUE TO CANCER. IT IS THE SPECIFIC AIM OF THIS PROJECT TO (1) SYNTHESIZE AND STUDY THE DETAILED ANTI-NOCICEPTIVE, PHARMOCOLOGICAL PROFILE OF FOUR CAREFULLY SELECTED NITROGEN ANALOGS WHICH HAVE THE PHENYLETHYLAMINE MOIETIES FOUND IN NARCOTIC LIKE ANALGESICS, AND (2) CHOOSE ONE OF THESE FOR FOLLOW-UP, IN-DEPTH STUDY AS A POTENTIAL MARKET-ABLE UNIQUE PRODUCT FOR USE IN A VARIETY OF DIFFERENT KINDS OF PAIN.