Anesthetic use of N-phenyl-N-(4-piperidinyl)amides

• US 5,466,700 A
• Filed: 08/30/1993
• Issued: 11/14/1995
• Est. Priority Date: 08/30/1993
• Status: Expired due to Term

• Current Assignee: Bioniche Teoranta
• Original Assignee: Glaxo Wellcome Incorporated (GlaxoSmithKline PLC)
• Inventors: Fox, Anthony W., Batenhorst, Randal L.
• Primary Examiner(s): Goldberg, Jerome D.
• Application Number:
  US08/114,032
• Time in Patent Office: 806 Days
• Field of Search: 514/327, 514/329
• US Class Current: 514/329
• CPC Class Codes: A61K 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl

Abstract

The use of particular opioids to induce and maintain anesthesia and conscious sedation is disclosed. The opioids used in the method of the present invention relate to the anesthetic action of the N-phenyl-N-(4-piperidinyl)amides as disclosed in U.S. Pat. No. 5,019,583 to Feldman, et al.

Claims

1. A method for providing anesthesia in a mammal comprising administering to such mammal a compound having the Formula (I):

##STR2## wherein X is a member selected from the group consisting of alkoxycarbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxycarbonyl-lower alkyl, and (C_1-2)alkoxy-(C_1-2)alkoxycarbonyl-lower alkyl;

Ar is a member selected from the group consisting of phenyl and mono-,di- and tri-substituted phenyl, wherein each substituent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;

R is a member selected from the group consisting of lower alkyl and lower alkoxy-lower alkyl;

R¹ is a member selected from the group consisting of hydrogen and lower alkoxycarbonyl; and

R² is a member selected from the group consisting of hydrogen and methyl; and

the optically active and cis-trans isomers thereof and the acid addition salts thereof;

said compound being administered to said mammal in an amount in excess of an amount effective for analgesia in order to induce or maintain anesthesia.

2. The method of claim 1, wherein said compound is administered parenterally.

3. The method of claim 1, wherein said compound is administered sublingually.

4. The method of claim 1, wherein said compound is administered transdermally.

5. The method of claim 1, wherein said compound is administered i.v. bolus.

6. The method of claim 5, wherein said compound is administered in an amount of about 8 to 20 g/kg.

7. The method of claim 6, wherein said compound is administered in an amount of about 0.1 to 3.0 g/kg/min.

8. The method of claim 1, wherein said compound is administered by continuous infusion.

9. The method of claim 1 wherein X is alkoxycarbonyl-lower alkyl.

10. The method of claim 1 wherein X is lower alkylcarbonyloxy-lower alkyl.

11. The method of claim 1 wherein X is alkenyloxycarbonyl-lower alkyl.

12. The method of claim 1 wherein X is alkoxycarbonyl-lower alkyl.

13. The method of claim 1 wherein Ar is phenyl or 2-fluorophenyl.

14. The method of claim 1 wherein R is ethyl.

15. The method of claim 1 wherein R¹ is methoxycarbonyl.

16. The method of claim 1 wherein said compound is selected from the group consisting of 5-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine]pentanoic acid, methyl ester;

2-[4-methoxycarbonyl-4-[(1-oxopropyl)phenylamino]-1-piperidine]ethyl acetate;

3-[4-(1-oxopropyl)-2-fluorophenylamino]-1-piperidine]-propanoic acid, methyl ester;

or 3-[4-methoxycarbonyl-4-[(oxopropyl)phenylamino]-1-piperidine]propanoic acid, vinyl ester and pharmaceutically acceptable acid addition salts thereof.

17. The method of claim 1 wherein said compound is 3-[4-methoxycarbony-4-[(1-oxopropyl)-phenylamino]-1-piperidine] propanoic acid, alkyl ester, and the pharmaceutically acceptable acid addition salts thereof.

18. The method of claim 1, wherein said mammal is a human.

19. The method of claim 18, wherein said compound of Formula (I) is administered in an amount at least 4 times in excess of its ED₅₀ for analgesia.

20. The method of claim 18, wherein said compound is administered in conjunction with a hypnotic in an effective amount to induce unconsciousness.

21. The method of claim 18, wherein said compound is administered in conjunction with a CNS depressant in an effective amount to induce unconsciousness.

22. The method of claim 18, wherein said compound is administered in an amount in excess of its ED₅₀ for analgesia.

23. The method of claim 22, wherein said compound is administered in conjunction with a hypnotic, an anxiolytic, or an inhaled agent being delivered in an amount less than 50% of its ED₅₀.

24. The method of claim 23, wherein said compound is administered in an effective amount to maintain anesthesia.

25. The method of claim 23, wherein said compound is administered alone or in conjunction with a hypnotic, an anxiolytic or an inhaled anesthetic agent in an amount such that upon discontinuing administration of said compound, said mammal recovers from anesthesia or sedation in less than 15 minutes.

26. The method of claim 25, wherein said hypnotic, anxiolytic and/or inhaled agent is administered in an amount such that upon discontinuing administration of said compound of Formula (I), said mammal recovers from anesthesia or sedation in less than 15 minutes.

27. A method for providing conscious sedation in a mammal comprising administering to such mammal a compound having the Formula (I):

##STR3## wherein X is a member selected from the group consisting of alkoxycarbonyl-lower alkyl, lower alkyl-carbonyloxy-lower alkyl, alkenyloxycarbonyl-lower alkyl, and (C_1-2)alkoxy-(C_1-2)alkoxycarbonyl-lower alkyl;

Ar is a member selected from the group consisting of phenyl and mono-,di- and tri-substituted phenyl, wherein each substituent is independently selected from the group consisting of halo, lower alkyl, lower alkoxy and trifluoromethyl;

R is a member selected from the group consisting of lower alkyl and lower alkoxy-lower alkyl;

R¹ is a member selected from the group consisting of hydrogen and lower alkoxycarbonyl; and

R² is a member selected from the group consisting of hydrogen and methyl; and

the optically active and cis-trans isomers thereof and the acid addition salts thereof;

said compound being administered to said mammal in an amount in excess of an amount effective for analgesia in order to induce or maintain conscious sedation.