6 211 201

6,211,201 Title:

Multivalent salts of pyridostigmine and related compounds

A quaternary ammonium cholinergic agent is complexed with a multivalent anion, or with multiple monovalent anions. The complex may be administered orally to a patient to treat pain, or for some other purpose. Numerous modifications are contemplated, including modifications to the ring structure of the compound, substitution and functionalization of the ring. Other contemplated modifications include the use of different anions, including various monovalent and polyvalent anions, and both organic and inorganic anions. The compounds have utility as cholinergic agents, and especially in the treatment of mysasthenia gravis, chest pain, and carpal tunnel syndrome.

We claim:

1. A pharmaceutically effective cholinergic compound having a plurality of carbamate chemical groupings according to the formula, [Y--R--O--CO--NR.sub.1 R.sub.2 ].sup.+, the groupingscovalently bound together in any of the following ways:

(a) through the nitrogen atom alpha to the carbamate carbonyl; and

(b) through a quaternary nitrogen atom in the ring structure of R;

wherein R is a ring or ring system, Y is alkyl, substituted alkyl, aryl, substituted aryl, aralkyl, substituted aralkyl, or NR.sub.3 R.sub.4 R.sub.5 where R.sub.1, R.sub.2, R.sub.3, R.sub.3, R.sub.4 and R.sub.5 are independently H, alkyl,substituted alkyl, aryl, or substituted aryl;

wherein all atoms external to and which covalently link two Rs have a neutral charge.

2. The compound of claim 1 wherein R is a six member heterocycle.

3. The compound of claim 1 wherein R is a six member heterocycle and Y is covalently bonded to R at a Nitrogen.

4. The compound of claim 1 wherein R is pyrimidine.

5. The compound of claim 1 wherein R is aza pyrimidine.

6. The compound of claim 1 wherein R is phenyl and Y is NR.sub.3 R.sub.4 R.sub.5.

7. The compound of claim 1 wherein R is a five member heterocycle.

8. The compound of claim 1 further containing tribromide.

9. The compound of claim 1 further containing an anion selected from the group consisting of carbonate, nitrate, and sulfate.

10. The compound of claim 1 further containing an anion selected from the group consisting of hydrogen phosphate, phosphite, and phosphate.

11. The compound of claim 1 further containing an organic acid anion.

12. The compound of claim 1 further containing an anion selected from the group consisting of carbonate, nitrate, sulfate, hydrogen phosphate, phosphite, phosphate, and an organic acid anion.

13. The compound of claim 1 wherein the groupings are covalently bound through an aliphatic chain of one to ten atoms.

14. The compound of claim 1 wherein the groupings are covalently bound through an aliphatic chain of one to ten atoms, and further containing an anion selected from the group consisting of carbonate, nitrate, sulfate, hydrogen phosphate,phosphite, phosphate, and an organic acid anion.

15. A method of treating a condition responsive to a cholinergic agent comprising administering to a patient an effective amount of the compound of claim 1.

16. A method of treating mysasthenia gravis comprising administering to a patient an effective amount of the compound of claim 1.

17. A method of treating carpal tunnel syndrome comprising administering to a patient an effective amount of the compound of claim 1.

18. The compound according to claim 1 which dissociates under physiologic conditions to produce Pyridostigmine.

19. The compound according to claim 1 which dissociates under physiologic conditions to produce Neostigmine.

20. The compound according to claim 1 which dissociates under physiologic conditions to produce Edrophonium.