Screening and therapeutic methods for promoting wakefulness and sleep

• US 20020037533A1
• Filed: 08/17/2001
• Published: 03/28/2002
• Est. Priority Date: 04/28/2000
• Status: Active Grant

• 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
• Granted Patent: US 6,884,596 B2
• Time in Patent Office: Days
• US Class Current: 435/7.1
• 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) providing a compound that is a PrRP receptor agonist; and

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

2. The method of claim 1, wherein step (a) comprises contacting a PrRP receptor with one or more candidate compounds under conditions wherein PrRP promotes a predetermined signal, identifying a compound that promotes said predetermined signal, and providing said compound.

3. The method of claim 2, wherein said predetermined signal is selected from the group consisting of calcium ion mobilization and arachadonic acid metabolite release.

4. The method of claim 2, wherein said PrRP receptor is GPR10.

5. The method of claim 2, wherein said PrRP receptor is contacted with greater than about 100 candidate compounds.

6. The method of claim 2, wherein said PrRP receptor is contacted with greater than about 10⁵ candidate compounds.

7. The method of claim 1, wherein step (a) comprises contacting a PrRP receptor with one or more candidate compounds under conditions wherein PrRP binds to said PrRP receptor, identifying a compound that binds to said PrRP receptor, and providing said compound.

8. The method of claim 7, wherein said PrRP receptor is GPR10.

9. The method of claim 7, wherein said PrRP receptor is contacted with greater than about 100 candidate compounds.

10. The method of claim 7, wherein said PrRP receptor is contacted with greater than about 10⁵ candidate compounds.

11. The method of claim 1, wherein step (a) comprises 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, identifying a compound that promotes said interaction, and providing said compound.

12. The method of claim 11, wherein said AMPA receptor associated protein is selected from the group consisting of GRIP, GRIP2 and PICK1.

13. 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.

14. 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, a rat and a mouse.

17. The method of claim 16, wherein step (a) comprises contacting a PrRP receptor with one or more candidate compounds under conditions wherein PrRP promotes a predetermined signal, identifying a compound that reduces said predetermined signal, and providing said compound.

18. The method of claim 17, wherein said contacting is performed in the presence of PrRP.

19. The method of claim 17, wherein said predetermined signal is selected from the group consisting of calcium ion mobilization and arachadonic acid metabolite release.

20. The method of claim 17, wherein said PrRP receptor is GPR10.

21. The method of claim 17, wherein said PrRP receptor is contacted with greater than about 100 candidate compounds.

22. The method of claim 17, wherein said PrRP receptor is contacted with greater than about 10⁵ candidate compounds.

23. The method of claim 16, wherein step (a) comprises contacting a PrRP receptor with one or more candidate compounds under conditions wherein PrRP binds to said PrRP receptor, identifying a compound that reduces binding of said PrRP to said PrRP receptor, and providing said compound.

24. The method of claim 23, wherein said contacting is performed in the presence of PrRP.

25. The method of claim 23, wherein said PrRP receptor is GPR10.

26. The method of claim 23, wherein said PrRP receptor is contacted with greater than about 100 candidate compounds.

27. The method of claim 23, wherein said PrRP receptor is contacted with greater than about 0~ 5candidate compounds.

28. The method of claim 16, wherein step (a) comprises 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, identifying a compound that reduces said interaction, and providing said compound.

29. The method of claim 28, wherein said contacting is performed in the presence of PrRP.

30. The method of claim 28, wherein said AMPA receptor associated protein is selected from the group consisting of GRIP, GRIP2 and PICK1.

31. The method of claim 16, wherein the ability of said compound to promote sleep is determined by a method selected from the group consisting of EEG measurement, EMG measurement and wake time measurement.

32. The method of claim 16, wherein the ability of said compound to promote sleep is determined by administering said compound to a mammal selected from the group consisting of a human, a non-human primate, a rat and a mouse.

15. A method of promoting wakefulness in a mammal, comprising administering to a mammal an effective amount of a PrRP receptor agonist.

16. A method of screening for a compound for promoting sleep in a mammal, comprising:

(a) providing a compound that is a PrRP receptor antagonist; and

(b) determining the ability of said compound to promote sleep.

33. A method of promoting sleep in a mammal, comprising administering to a mammal an effective amount of a PrRP receptor antagonist.