Modulation of central nervous system (CNS) dipeptidyl peptidase IV (DPIV) -like activity for the treatment of neurological and neuropsychological disorders
The present invention discloses a method for therapeutically treating an animal, including a human, for psychosomatic, depressive and neuropsychiatric diseases, such as anxiety, depression, insomnia, schizophrenia, epilepsy, spasm and chronic pain. Administration of a suitable DP IV inhibitor causes the reduction of activity in the enzyme dipeptidyl peptidase (DP IV or CD 26) or of DP IV-like enzyme activity in the brain of mammals and leads as a causal consequence to a reduced degradation of the neuropeptide Y (NPY) and similar substrates by DP IV and DP IV-like enzymes. Such treatment will result in a reduction or delay in the decrease of the concentration of functionally active neuronal NPY (1–36). As a consequence of the resulting enhanced stability of the endogenous NPY (1–36) caused by the inhibition of DP IV activity, NPY activity is prolonged thereby resulting among other things in functionally active NPY Y1 receptor activity thereby facilitating anti-depressive, anxiolytic, analgesic, anti-hypertension and other neurological effects.
1. A method of treating anxiety comprising introducing into the central nervous system a therapeutically effective amount of an inhibitor of dipeptidyl peptidase IV enzyme formulated in combination with neuropeptide Y.
2. The method of claim 1 wherein said introducing of said inhibitor of dipeptidyl peptidase IV enzyme in combination with neuropeptide Y is parenteral.
3. The method of claim 1 , wherein said inhibitor of dipeptidyl peptidase IV enzyme is selected from the group con g of N—(N′-substituted glycyl)-2-cyanopyrrolidines, L-threo-isoleucyl thiazolidine, L-threo-isoleucyl pyrrolidine, L-allo-isoleucyl thiazolidine and L-allo-isoleucyl pyrrolidine.