Screening and therapeutic methods for promoting wakefulness and sleep

• US 6,884,596 B2
• Filed: 08/17/2001
• Issued: 04/26/2005
• Est. Priority Date: 04/28/2000
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Lin, Steven, Civelli, Olivier
• Primary Examiner(s): Kemmerer, Elizabeth
• Assistant Examiner(s): DeBerry, Regina M.
• Application Number:
  US09/932,161
• Publication Number:
  US 20020037533A1
• Time in Patent Office: 1,348 Days
• Field of Search: 435/7.8, 435/7.1, 514/2, 514/21, 514/44, 436/501, 436/567, 424/130.1, 530/300, 530/350, 530/399
• US Class Current: 435/7.8
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 5/02 of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/04 for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

The invention provides methods of screening for a compound for promoting wakefulness in a mammal. The method is practiced by providing a compound that is a PrRP receptor agonist and determining the ability of the compound to promote wakefulness. Also provided by the invention are methods of screening for a compound for promoting sleep in a mammal. The methods are practiced by providing a compound that is a PrRP receptor antagonist and determining the ability of the compound to promote sleep. In addition, the invention provides a method of promoting wakefulness in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor agonist. The invention further provides a method of promoting sleep in a mammal. The method is practiced by administering to a mammal an effective amount of a PrRP receptor antagonist.

Claims

1. A method of screening for a compound for promoting wakefulness in a mammal, comprising:

(a) contacting a PrRP receptor with one or more candidate compounds under conditions wherein PrRP promotes interaction of PrRP receptor with an AMPA receptor associated protein;

(b) identifying a compound that promotes said interaction;

(c) providing said compound, and

(d) determining the ability of said compound to promote wakefulness.

2. The method of claim 1, wherein said AMPA receptor associated protein is selected from the group consisting of GRIP, GRIP2 and PICK1.

3. The method of claim 1, wherein the ability of said compound to promote wakefulness is determined by a method selected from the group consisting of EEG measurement, EMG measurement and wake time measurement.

4. The method of claim 1, wherein the ability of said compound to promote wakefulness is determined by administering said compound to a mammal selected from the group consisting of a human, a non-human primate, rat and a mouse.