Retro-inverso analogs of spadin display increased antidepressant effects
Compositions, pharmaceutical compositions and biodegradable pharmaceutical compositions containing at least one analog of spadin or at least one analog of a propeptides of spadin or mixtures thereof are described. Methods for treating depression using the analogs of spadin or analogs of propeptides of spadin or mixtures thereof, as well as methods for blocking TREK-1 channel activity are also disclosed.
1. A composition comprising at least one analog of spadin or at least one analog of a propeptide of spadin or mixtures thereof of said at least one analog, wherein said at least one analog is a retro-inverso peptide and is end-capped, and is selected from the group of: Ac-rlGwsvGipGswrplpa-NH 2 (SEQ ID NO:4), Ac-rlGwsvGi-NH 2 (SEQ ID NO:7), Ac-rlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:9), Ac-rlGwsvGipGswrplpaappppa-NH 2 (SEQ ID NO:11), Ac-rrwrGGrpfaGGaaaarlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:13), Ac-rlawsvaipaswrplpa-NH 2 (SEQ ID NO: 15), c(rlGwsvGipGswrplpa) (SEQ ID NO:20), c(rlGwsvGipGswrplparlGwsvGipGswrplpa) (SEQ ID NO:21) and mixtures thereof.
2. A method for blocking TREK-1 channel activity, said method comprising administering to an animal an effective amount of the pharmaceutical composition according to claim 1 .
3. A pharmaceutical composition comprising, in a pharmaceutically acceptable vehicle, at least one analog of spadin or at least one analog of a propeptide of spadin or mixtures thereof of said at least one analog, wherein said at least one analog is a retro-inverso peptide and is end-capped, and is selected from the group of: Ac-rlGwsvGipGswrplpa-NH 2 (SEQ ID NO:4), Ac-rlGwsvGi-NH 2 (SEQ ID NO:7), Ac-rlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:9), Ac-rlGwsvGipGswrplpaappppa-NH 2 (SEQ ID NO:11), Ac-rrwrGGrpfaGGaaaarlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:13), Ac-rlawsvaipaswrplpa-NH 2 (SEQ ID NO: 15), c(rlGwsvGipGswrplpa) (SEQ ID NO:20), c(rlGwsvGipGswrplparlGwsvGipGswrplpa) (SEQ ID NO:21) and mixtures thereof.
4. A biodegradable pharmaceutical composition comprising at least one analog of spadin or at least one an analog of a propeptide of spadin or mixtures thereof of said at least one analog in a biodegradable slow release vehicle,
wherein the at least one analog of spadin or the at least one analog of a propeptide of spadin or mixtures thereof of said at least one analog is a retro-inverso peptide and is end-caped, and is selected from the group of: Ac-rlGwsvGipGswrplpa-NH 2 (SEQ ID NO:4), Ac-rlGwsvGi-NH 2 (SEQ ID NO:7), Ac-rlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:9), Ac-rlGwsvGipGswrplpaappppa-NH 2 (SEQ ID NO:11), Ac-rrwrGGrpfaGGaaaarlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:13), Ac-rlawsvaipaswrplpa-NH 2 (SEQ ID NO: 15), c(rlGwsvGipGswrplpa) (SEQ ID NO:20), c(rlGwsvGipGswrplparlGwsvGipGswrplpa) (SEQ ID NO:21) and mixtures thereof.
5. A biodegradable pharmaceutical composition comprising Ac-rlGwsvGipGswrplpa-NH 2 (SEQ ID NO:4) or Ac-rlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:9) or Ac-rlGwsvGipGswrplpa-NH 2 (SEQ ID NO:4) and Ac-rlGwsvGipGswrplpaappppadlrdq-NH 2 (SEQ ID NO:9) in a biodegradable slow release vehicle.