Method of using exendin and GLP-1 to affect the central nervous system

• US 5,846,937 A
• Filed: 03/03/1997
• Issued: 12/08/1998
• Est. Priority Date: 03/03/1997
• Status: Expired due to Fees

• Current Assignee: 1149336 Ontario Inc.
• Original Assignee: 1149336 Ontario Inc.
• Inventors: Drucker, Daniel J.
• Primary Examiner(s): Allen, Marianne P.
• Application Number:
  US08/811,066
• Time in Patent Office: 645 Days
• Field of Search: 514/2, 514/12, 530/350, 530/324
• US Class Current: 514/17.5
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 2267/0356 Animal model for processes and diseases of the central nervous system, e.g. stress, learning, schizophrenia, pain, epilepsy
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 38/2278 Vasoactive intestinal peptide [VIP]; Related peptides (e.g. Exendin)
• CPC Class Codes: A61K 38/26 Glucagons
• CPC Class Codes: C12N 15/8509 for producing genetically modified animals, e.g. transgenic

Abstract

Agonists of the incretin GLP-1 have been found to have a sedative or anxiolytic effect on the mammalian central nervous system. Additionally, exendin has been found to have an independent sedative effect on the mammalian central nervous system. Conversely, antagonists of GLP-1 increase nervous system activity. The invention relates, in one aspect, to the use of GLP-1 agonists and antagonists to affect the arousal state of the mammalian central nervous system. The invention also relates to novel transgenic mammals in which the GLP-1 receptor gene has been disrupted.

Claims

1. A method of sedating a mammalian subject in need thereof, comprising administering exendin-3, exendin-4, GLP-1, or an agonist of the GLP-1 receptor to the subject in an amount sufficient to produce a sedative or anti-anxiolytic effect on the subject.

2. The method of claim 1, wherein exendin-4 is administered to the subject.

3. The method of claim 1 or 2, wherein the exendin-3, exendin-4, GLP-1, or agonist of the GLP-1 receptor is administered intracerebroventricularly.

4. The method claim 3, wherein the mammalian subject is a human.

5. The method of claim 1 or 2, wherein the exendin-3, exendin-4, GLP-1, or agonist of the GLP-1 receptor is administered orally, subcutaneously, intramuscularly, or intravenously.

6. The method of claim 5, wherein the mammalian subject is a human.

7. The method of claim 2, wherein exendin-4 is administered to the subject in the range of 50 to 250 nanoMoles/kg body weight/minute intravenously, or 5 to 200 μ

M/kg body weight subcutaneously.

8. The method of claim 1, wherein the mammalian subject is suffering from an abnormality resulting in anxiety, aggression, psychosis, seizures, panic attacks, hysteria, or sleep disorders.

9. The method of claim 1, wherein GLP-1 is administered to the subject in the range of 1 to 5 pM/kg body weight/minute intravenously, or 0.1 to 5 nanoMoles/kg body weight subcutaneously.

10. The method of claim 1, 2, 8, 7 or 9, wherein the mammalian subject is a human.