Chimeric gaba receptor

The hGABABR1a/GABABR2 CHO cell line deposited at the Belgian Coordinated Collections of Microorganisms (BCCM) as CHO-K1 h-GABA-b R1a/R2 clone on Aug. 22, 2003 with the accession number LMBP 6046CB.

A method to identify GABAB receptor agonists said method comprising,

• a) exposing cells expressing a functional GABAB receptor, wherein such cells do not normally express the GABAB receptor, to a labeled agonist of GABAB in the presence and absence of the test compound, and
• b) determine the binding of the labeled agonist to said cells,
• where if the amount of binding of the labeled agonist is less in the presence of the test compound, then the compound is a potential agonist of the GABAB receptor.

A method according to claim 10 wherein the labeled agonist is selected from the group consisting of 3H-GABA, 3H-baclofen and 3H-3-APPA.

A method to identify GABAB receptor antagonists said method comprising,

• a) exposing cells expressing a functional GABAB receptor, wherein such cells do not normally express the GABAB receptor, to a labeled antagonist of GABAB in the presence and absence of the test compound, and
• b) determine the binding of the labeled antagonist to said cells,
• where if the amount of binding of the labeled antagonist is less in the presence of the test compound, then the compound is a potential antagonist of the GABAB receptor.

A method for identifying compounds that have the capability to modulate GABAB receptor activity, said method comprising;

• a) contacting cells expressing a functional GABAB receptor, wherein said cells do not normally express a functional GABAB receptor, with at least one reference compound, under conditions permitting the activation of the GABAB receptor;
• b) contacting the cells of step a) with a test compound, under conditions permitting the activation of the GABAB receptor, and
• c) determine whether said test compound modulates the GABAB receptor activity compared to the reference compound.

Use of a compound of formula (I) in the manufacture of a medicament to reduce transient lower esophagal sphincter relaxations (TLESR).

A compound of formula (I) wherein =Z1-Z2=Z3-Z4=represents (a), (b) or (d), more preferably those compounds of formula (I) wherein =Z1-Z2=Z3Z4=represents (d).