Patent ID: 7945392

Claim:
A computer-implemented method for screening a receptor antagonist test composition for potential efficacy in treatment of schizophrenia, the method comprising causing a computer to execute instructions for: (a) creating a first computer model representative of a volume of disease-afflicted neural tissue comprising a plurality of interconnected modeled neurons; wherein for each modeled neuron the model quantitatively simulates spatially compartmentalized conductance of a plurality of ion channels and spatially compartmentalized activity of a plurality of receptors; (b) modifying the first computer model to simulate exposure of each of the receptors R in the disease-afflicted neural tissue to the test composition by (1) defining (i) an antagonist test composition concentration B, (ii) an antagonist test composition dissociation constant K B , (iii) a naturally present agonist concentration A, (iv) a naturally present agonist dissociation constant K A , (v) a receptor concentration R t , (vi) an equilibrium dissociation constant K A , and (vii) an efficacy constant K E ; (2) calculating for each receptor R in the model a fractional occupancy of the receptor by naturally present agonist A in the presence of antagonist test composition B using equation (1): [ A · R ] [ R t ] = [ A ] [ A ] + K A ⁡ ( 1 + [ B ] / K B ) ( 1 ) wherein A·R represents a concentration of an agonist-receptor complex; (3) using the value of A·R from step (2), calculating a test composition response ratio E a /E m for each receptor in the model using equation (2): E a E m = [ A · R ] K E + [ A · R ] ( 2 ) wherein E a is a test composition response and E m is a maximal test composition response; and (4) combining results for each receptor in the model to provide an overall test composition efficacy; (c) providing an initial excitation to the first modified computer model; (d) determining a first outcome indicative of a response of the first modified computer model to the initial excitation and the test composition, wherein the first outcome is representative of the efficacy of the test composition at treating the disorder; and (e) providing an output indicative of the efficacy of the test composition at treating the disorder to a physical memory, a mass storage device, a removable media, or a user interface device.