Compositions and methods for respiratory depression and related side effects of mu-opioid compounds

 

(57) Abstract:

The invention relates to medicine, namely the method of reducing, treating or preventing mediated drug respiratory depression, muscle rigidity or nausea/vomiting in an animal related to the introduction of specified animal mixed Delta/mu opioid agonist or drugs, mediating respiratory depression, in which the animal receiving the specified medication, administered an effective amount of the compound-agonist Delta-receptor formula I. the Method allows you to more effectively reduce the specified respiratory depression, muscle rigidity or nausea/vomiting. 2 C. and 17 C.p. f-crystals, 2 ill., 1 PL.

Description text in facsimile form (see drawings). Those

1. Method of reducing, treating or preventing mediated drug respiratory depression, muscle rigidity or nausea/vomiting in an animal related to the introduction of specified animal drugs, mediating respiratory depression, in which the animal receiving the specified medication, mediating respiratory depression, introducing an effective amount of the compound - agonist Delta-receptor formula


or its pharmaceutically acceptable complex ester or salt.

2. The method according to p. 1, wherein the drug mediating respiratory depression, is an agonist at mu-receptor.

3. The method according to p. 2, wherein the agonist Delta-receptor is administered in conjunction with an agonist of mu-receptor.

4. The method according to p. 3, wherein said agonist Delta-receptor contains (+)-3-((R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide, as specified agonist at mu receptor selected from the group consisting of anesthetic compounds and analgesic compounds.

5. The method according to p. 1, wherein the specified connection agonist Delta-receptor is a

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6. The method according to p. 1, in which analgesia is mediated drug mediating respiratory depression, with a therapeutic index is the ratio of the ED50for respiratory depression to the ED50for analgesia, significantly exceeding therapeutic index of fentanyl, in which the animal is administered an amount of (+)-3-((R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide, which is effective is own by p. 6, in which the specified therapeutic index substantially greater than 4.5.

8. Pharmaceutical composition comprising: (1) an effective amount of bioactive compounds mediating respiratory depression, muscle rigidity and/or nausea/vomiting as its adverse effect; and (2) connection - agonist Delta-receptor formula

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where R1represents a C1-C6alkyl;

R represents a C1-C6alkyl or 6-membered aromatic ring, optionally having halogen Deputy,

or its pharmaceutically acceptable ester or salt.

9. The pharmaceutical composition according to p. 8 also containing pharmaceutically acceptable carrier.

10. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor represents a (-)-4-((R)--((2R, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N, N-diethylbenzamide or its pharmaceutically acceptable salt.

11. The pharmaceutical composition under item 8, in which the bioactive compound contains opiate connection.

12. The pharmaceutical composition under item 8, in which the bioactive compound contains opiate analgesic compounds connection.

14. The pharmaceutical composition according to p. 13, in which the mu-opioid compound and agonist Delta-receptor are administered together.

15. The pharmaceutical composition according to p. 14, in which the specified Delta agonist-receptor contains (+)-3-(R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide.

16. The pharmaceutical composition according to p. 14, in which the specified agonist at mu receptor selected from the anesthetic compounds and analgesic compounds.

17. The pharmaceutical composition according to p. 14, in which the specified agonist at mu receptor selected from the group consisting of Alfentanil, fentanyl, morphine and its analogs.

18. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor is a

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19. The pharmaceutical composition under item 8, in which the connection agonist Delta-receptor is a (+)-3-((R)--((2S, 5R)-4-allyl-2,5-dimethyl-1-piperazinil)-3-hydroxybenzyl)-N-(3-forfinal)-N-methylbenzamide.

 

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