Methods of use comprising deuterated pyrazino[2,1-a]isoquinolines

1. A method of disrupting cell permeability to calcium ions in a parasitic cell, comprising contacting said cell with a compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 is hydrogen or fluorine;

Z 2 is hydrogen, deuterium, or fluorine;

Z 3 is deuterium;

Z 4 is fluorine;

m is 2, 4, 6, 8 or 10; and

n is 0 or 2;

provided that:

the sum of m and n does not exceed 10.

2. The method of claim 1 , wherein 2, 4, 6, 8 or 10 geminal Z 3 are present.

3. The method of claim 1 , wherein Z 2 is hydrogen.

4. The method of claim 1 , wherein Z 2 is deuterium.

5. The method of claim 1 , wherein 2 geminal Z 4 are present.

6. The method of claim 1 , wherein the compound is selected from any one of the following compounds:

or a pharmaceutically acceptable salt thereof.

7. The method of claim 1 , wherein the compound is selected from the following compounds:

or a pharmaceutically acceptable salt thereof.

8. A method of treating a disease or condition selected from schistosoma infections, infections due to Clonorchis sinensis or Opisthorchis viverrini ; cysticercosis; neurocysticercosis; and malaria, in a patient in need thereof comprising the step of administering to said patient an effective amount of a compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 is hydrogen or fluorine;

Z 2 is hydrogen, deuterium, or fluorine;

Z 3 is deuterium;

Z 4 is fluorine;

m is 2, 4, 6, 8 or 10; and

n is 0 or 2;

provided that:

the sum of m and n does not exceed 10.

9. The method of claim 8 , wherein 2, 4, 6, 8 or 10 geminal Z 3 are present.

10. The method of claim 8 , wherein Z 2 is hydrogen.

11. The method of claim 8 , wherein Z 2 is deuterium.

12. The method of claim 8 , wherein 2 geminal Z 4 are present.

13. The method of claim 8 , wherein the compound is selected from any one of the following compounds:

or a pharmaceutically acceptable salt thereof.

14. The method of claim 8 , wherein the compound is selected from the following compounds:

or a pharmaceutically acceptable salt thereof.

15. A method of treating infections due to nematodes, sarcocystis, neosporosis, toxoplasmosis, isosporosis; parasitic infection of farm and domestic animals selected from cestodes, trematodoses, nematodoses and pests invasions; toxoplasmosis, African trypanosomiasis, Chagas disease, leishmaniasis, schistosomiasis, helminthosis, fascioliasis, paragonimiasis, and tapeworms in a mammal in need thereof comprising the step of administering to said mammal an effective amount of a compound of Formula Ia:

or a pharmaceutically acceptable salt thereof, wherein:

Z 1 is hydrogen or fluorine;

Z 2 is hydrogen, deuterium, or fluorine;

Z 3 is deuterium;

Z 4 is fluorine;

m is 2, 4, 6, 8 or 10; and

n is 0 or 2;

provided that:

the sum of m and n does not exceed 10.

16. The method of claim 15 , wherein 2, 4, 6, 8 or 10 geminal Z 3 are present.

17. The method of claim 15 , wherein Z 2 is hydrogen.

18. The method of claim 15 , wherein Z 2 is deuterium.

19. The method of claim 15 , wherein 2 geminal Z 4 are present.

20. The method of claim 15 , wherein the compound is selected from any one of the following compounds:

or a pharmaceutically acceptable salt thereof.

21. The method of claim 15 , wherein the compound is selected from the following compounds:

or a pharmaceutically acceptable salt thereof.