A neuropeptide S receptor antagonist comprising a compound of structure or a pharmaceutically acceptable salt thereof: where the dotted lines denote a saturated or unsaturated bond, with the proviso that either all dotted lines denote an unsaturated bond, only the dotted line between e and f is an unsaturated bond or none of the dotted lines denote an unsaturated bond; X 1 is either CH, CH 2, N or N-R 3 and X 2 is CH when X 1 is N, X 2 is CH 2 when X 1 is N-R 3, X 2 is N when X 1 is CH, and X 2 is N-R 3 when X 1 is CH 2; m is 0 or 1; the wavy lines represent bonds connected to carbons having cis- or trans- configuration; Y 1 is O or S; Y 2 is O, N, or CH 2; R 1 and R 2 are jointly structure: where p is 0 or 2 if ring B is present and p is 2 if ring B is not present; or R 1 and R 2 are each independently methyl alcohol, phenyl, straight chain or branched C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl or heterocycle, substituted aryl, thiophene, furan, or one of the following structures: where Y 3 may be at any position on the ring and is H, halogen, OH, C 1-4 alkyl, C 1-4 hydroxyalkyl, or CF 3; or and R 3 is -C(=NH)NH 2, -CONH(CH 2) 3 CH 3, -CONH(CH 2) 4 CH 3, or where R 6 may be at any position on the ring and is H, NH 2, NHCOCH 3, -OCH 2 CH 3, NHCO(CH 2) 4 CH 3, N(CH 3) 2, NHCOOC(CH 3) 3, halogen, wherein n is 0 to 3; or R 3 is one of the following structures: where R 5 is C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, heterocycle, substituted aryl, substituted thiophene, furan, pyrrole, a natural amino acid side chain, or an unnatural amino acid side chain selected from the group consisting of Norleucine, Cyclohexylalanine, Homocyclohexylalanine, Cyclohexylglycine, 2-amino isobutyric acid, 3-Cyclopentylalanine, Norvaline, and homophenylalanine; and R 4 is C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, heterocycle, substituted aryl, substituted thiophene, furan, pyrrole, or H; or where Y 4 may be O or S with the proviso that the compound is not 1,1-diphenyl-furo[3,4-c]pyridin- -3-one, 3,3-diphenyl-furo[3,4-c]pyridin-1 -one or 3,3-di-(4-hydroxyphenyl)-furo[3,4-c]pyridin-1- -one. X 1 is either CH, CH 2, N or N-R 3 and X 2 is CH when X 1 is N, X 2 is CH 2 when X 1 is N-R 3, X 2 is N when X 1 is CH, and X 2 is N-R 3 when X 1 is CH 2; m is 0 or 1; the wavy lines represent bonds connected to carbons having cis- or trans- configuration; Y 1 is O or S; Y 2 is O, N, or CH 2; R 1 and R 2 are jointly structure: where p is 0 or 2 if ring B is present and p is 2 if ring B is not present; or where p is 0 or 2 if ring B is present and p is 2 if ring B is not present; or R 1 and R 2 are each independently methyl alcohol, phenyl, straight chain or branched C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl or heterocycle, substituted aryl, thiophene, furan, or one of the following structures: where Y 3 may be at any position on the ring and is H, halogen, OH, C 1-4 alkyl, C 1-4 hydroxyalkyl, or CF 3; or and R 3 is -C(=NH)NH 2, -CONH(CH 2) 3 CH 3, -CONH(CH 2) 4 CH 3, or where R 6 may be at any position on the ring and is H, NH 2, NHCOCH 3, -OCH 2 CH 3, NHCO(CH 2) 4 CH 3, N(CH 3) 2, NHCOOC(CH 3) 3, halogen, wherein n is 0 to 3; or R 3 is one of the following structures: where R 5 is C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, heterocycle, substituted aryl, substituted thiophene, furan, pyrrole, a natural amino acid side chain, or an unnatural amino acid side chain selected from the group consisting of Norleucine, Cyclohexylalanine, Homocyclohexylalanine, Cyclohexylglycine, 2-amino isobutyric acid, 3-Cyclopentylalanine, Norvaline, and homophenylalanine; and R 4 is C 1-8 alkyl, C 3-6 cycloalkyl, C 2-8 alkenyl, C 2-8 alkynyl, C 6-10 aryl, heterocycle, substituted aryl, substituted thiophene, furan, pyrrole, or H; or where Y 4 may be O or S with the proviso that the compound is not 1,1-diphenyl-furo[3,4-c]pyridin- -3-one, 3,3-diphenyl-furo[3,4-c]pyridin-1 -one or 3,3-di-(4-hydroxyphenyl)-furo[3,4-c]pyridin-1- -one. where Y 4 may be O or S with the proviso that the compound is not 1,1-diphenyl-furo[3,4-c]pyridin- -3-one, 3,3-diphenyl-furo[3,4-c]pyridin-1 -one or 3,3-di-(4-hydroxyphenyl)-furo[3,4-c]pyridin-1- -one.