Abstract: In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASP-2 inhibitory agent and a pharmaceutically acceptable carrier.

Abstract: Methods for screening specific biological endpoints that can be utilized to identify potential therapeutic agents for METH addiction. In one aspect of the invention, the methods involve reversal of behavioral sensitization and/or conditioned place preference in an animal previously treated with METH in the presence of a known amount of a 5-HT2A/2C antagonist or a selective 5-HT2C antagonist, and reversal of the electrophysiological endpoints in a METH-treated animal in the presence of a known amount of the 5-HT2A/2C antagonist or the selective 5-HT2C antagonist. Therapeutic treatment methods for reversing the set of biological endpoints that change in the METH drug addict using mirtazapine, SDZ SER 082, and related serotonin antagonists are also provided. The methods of the invention may be utilized in the identification of potential new therapies for multiple drugs of abuse.

Abstract: The present invention discloses novel 5-HT receptor binding agents of Formula 3, wherein X is —CH or —N—. Y is selected from the group consisting of —CR10R11, —NR12, —O—, —S—, —SO—, and —SO2—. R1 to R12 are various substituents selected to optimize the physicochemical and biological properties such as receptor binding, receptor selectivity, tissue penetration, lipophilicity, toxicity, bioavailability, and pharmacokinetics of compounds of Formula 3. These include hydrogen, alkyl, acyl, hydroxyl, hydroxyalkyl, aryl, amino, aminoalkyl, alkoxyl, aryloxyl, carboxyl, alkoxycarbonyl, halogen, cyano, and other suitable electron donating or electron withdrawing groups. R2 and R3, R3 and R4, or R5 and R6 may optionally be tethered together to form fused alicyclic or heterocyclic ring. R1 and R2, R4 and R5, or R6 and R7 may also optionally be tethered together to form spiro carbo- or heterocyclic ring.

Abstract: In one aspect, the invention provides methods of inhibiting the effects of lectin-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MAp19 inhibitory agent effective to inhibit lectin-dependent complement activation. In some embodiments, the MAp19 inhibitory agent inhibits cellular injury associated with lectin-mediated complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides MAp19 specific antibodies that do not bind to MASP-2 and methods of producing MAp19 specific antibodies. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MAp19 inhibitory agent and a pharmaceutically acceptable carrier.

Abstract: In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a living subject. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation. In some embodiments, the MASP-2 inhibitory agent inhibits cellular injury associated with MASP-2-mediated alternative complement pathway activation, while leaving the classical (C1q-dependent) pathway component of the immune system intact. In another aspect, the invention provides compositions for inhibiting the effects of lectin-dependent complement activation, comprising a therapeutically effective amount of a MASp-2 inhibitory agent and a pharmaceutically acceptable carrier.