Claims
- 1. A method for antagonizing neuromuscular blocking effects induced by therapeutic agents and physiological disorders in mammals, which comprises administering to said mammal an antagonizing-effective amount of a compound of the formula: ##STR5## wherein R.sub.2 and R.sub.2 are each hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aralkyl, cycloalkyl, cycloalkyl-lower alkyl or hydroxyalkyl, with the proviso that both are not hydrogen;
- R.sub.3 is hydrogen or lower alkyl; and
- R.sub.4 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, halogen or acyl; wherein the alkyl groups in alkyl per se, aralkyl, cycloalkyl-lower alkyl and hydroxyalkyl contain from 1 to 6 carbon atoms; the cycloalkyl groups in cycloalkyl per se and cycloalkyl-lower alkyl contain from 4 to 8 carbon atoms; the alkenyl and alkynyl groups contain from 2 to 6 carbon atoms; the acyl group contains from 1 to 6 carbon atoms; and the aryl groups in aryl per se and aralkyl contain from 6 to 10 carbon atoms; or a salt thereof with acid.
- 2. The method according to claim 1 wherein R.sub.1 and R.sub.2 are each selected from the group consisting of lower alkyl, aryl, and aralkyl,
- R.sub.3 and R.sub.4 are each hydrogen.
- 3. The method according to claim 2 wherein R.sub.1 and R.sub.2 are each lower alkyl.
- 4. The method according to claim 2 wherein R.sub.1 and R.sub.2 are each methyl.
- 5. The method of claim 4 wherein the compound is 1,1-diemethyl-3-(4-amino-3-pyridyl) urea.
- 6. The method of claim 1 wherein the therapeutic agent is selected from the group consisting of a nondepolarizing muscle relaxant, an antibiotic which inhibits neuromuscular transmission and magnesium.
- 7. The method of claim 6 wherein the muscle relaxant is curare, d-tubocurarine or pancuronium.
- 8. The method of claim 6 wherein the antibiotic is an aminoglycoside, polypeptide-type antibiotic, lincomycin or spectinomycin.
- 9. The method of claim 1 wherein the disorder is botulism A.
- 10. The method of claim 1 wherein the disorder is myasthenia gravis.
- 11. The method of claim 1 wherein the disorder is Eaton-Lambert Syndrome.
- 12. The method of claim 1 wherein the disorder is senile dementia (Altzheimer's type).
- 13. The method of claim 1 wherein the disorder is multiple sclerosis.
- 14. The method of claim 6 wherein the compound is administered intravenously.
- 15. The method of claim 14 wherein the compound is administered in an amount of from about 0.1 to 2.0 mg/kg.
- 16. The method of claim 9 wherein the compound is administered by intravenous infusion of about 0.1 to 2.0 mg/ml solution.
- 17. The method of claim 10 wherein the compound is administered intravenously, orally or rectally.
- 18. The method of claim 17 wherein, when administered intravenously, the compound is administered in an amount of from about 0.1-2.0 mg/kg.
- 19. The method of claim 17 wherein, when administered orally or rectally, the compound is administered in an amount of from about 0.3 to 6.0 mg/kg.
- 20. The method of claim 11 wherein the compound is administered intravenously, orally or rectally.
- 21. The method of claim 20 wherein, when administered intravenously, the compound is administered in an amount of from about 0.1 to 2.0 mg/kg.
- 22. The method of claim 20 wherein, when administered orally or rectally, the compound is present in an amount of from about 0.3-6.0 mg/kg.
- 23. The method of claim 12 wherein the compound is administered orally.
- 24. The method of claim 23 wherein the compound is in an amount of about 0.1 to 3.0 mg/kg.
- 25. The method of claim 13 wherein the compound is administered intravenously, orally or rectally.
- 26. The method of claim 25 wherein, when administered intravenously, the compound is administered in an amount of from about 0.1 to 2.0 mg/kg.
- 27. The method of claim 25 wherein, when administered orally or rectally, the compound is administered in an amount of from about 0.3 to 6.0 mg/kg.
- 28. A therapeutic composition for the antagonism of neuromuscular block which comprises a compound of the formula: ##STR6## at a unit dosage level of from about 0.1 to about 6.0 mg/kg. wherein R.sub.1 and R.sub.2 are each hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, aralkyl, cycloalkyl, cycloalkyl-lower alkyl or hydroxyalkyl, with the proviso that both are not hydrogen;
- R.sub.3 is hydrogen or alkyl; and
- R.sub.4 is hydrogen, lower alkyl, lower alkenyl, lower alkynyl, or halogen or acyl; wherein the alkyl groups in alkyl per se, aralkyl, cycloalkyl-lower alkyl and hydroxyalkyl contain from 1 to 6 carbon atoms; the cycloalkyl groups in cycloalkyl per se and cycloalkyl-lower alkyl contain from 4 to 8 carbon atoms; the alkenyl and alkynyl groups contain from 2 to 6 carbon atoms; the acyl group contains from 1-6 carbon atoms and the aryl groups in aryl per se and aralkyl contain from 6 to 10 carbon atoms;
- or a salt thereof with acid.
RELATED APPLICATIONS
This application is a continuation-in-part of copending U.S. Ser. No. 524,843, filed Aug. 19, 1983 now abandoned.
US Referenced Citations (14)
Non-Patent Literature Citations (2)
Entry |
Bowman et al., Pharmacological Actions of Aminopyridines and Related Compounds, Reviews in Pure and Applied Pharmacological Science, vol. 2, 317-371 (1981). |
Den Hertog et al., CA 100 61641q, 1984. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
524843 |
Aug 1983 |
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