Medicine combinations and treatment of restless leg syndrome

Abstract

Embodiments disclosed herein describe, amongst other things, dosage forms, compounds, compositions, pharmaceutical compositions that can be used in the treatment of, for example, restless leg syndrome.

1 . A method of treating restless leg syndrome or symptoms thereof in a subject comprising administering to the subject a pharmaceutical composition or a pharmaceutical dosage form comprising a NMDA antagonist; a CYP2D6 inhibitor; and an opioid agonist. 
     
     
         2 . The method of  claim 1 , wherein the subject suffers from augmentation of restless leg syndrome. 
     
     
         3 . The method of  claim 1 , wherein the opioid agonist is tramadol, morphine, oxycodone, oxymorphone, alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, papavereturn, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, proheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tilidine, or a pharmaceutically acceptable salt thereof. 
     
     
         4 . The method of  claim 1 , wherein the NMDA antagonist is chosen from one or more of dextromethorphan, a glycine antagonist, ifenprodil like compound, amantadine, MK-801 (dizocilpine; [5R,10S]-[+]-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine), ketamine, memantine, D-AP5 (D(−)-2-Amino-5-phosphonovaleric acid) and, CPP (3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid), or a pharmaceutically acceptable salt thereof, or any combination thereof. 
     
     
         5 . The method of  claim 1 , wherein the NMDA antagonist is dextromethorphan, or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The method of  claim 3 , wherein the NMDA antagonist is dextromethorphan, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 1 , wherein the CYP2D6 inhibitor is chosen from one or more of: quinidine, bupropion, cinacalcet, fluoxetine, paroxetine, duloxetine, sertraline, terbinafine, amiodarone, and cimetidine, or a pharmaceutically acceptable salt thereof, or any combination thereof. 
     
     
         8 . The method of  claim 1 , wherein the CYP2D6 inhibitor is quinidine, or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 3 , wherein the CYP2D6 inhibitor is quinidine, or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 6 , wherein the CYP2D6 inhibitor is quinidine, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 1 , wherein the pharmaceutical composition is formulated for simultaneous administration. 
     
     
         12 . The method of  claim 1 , wherein the ratio of the opioid agonist to NMDA antagonist is about 1:1 (wt:wt). 
     
     
         13 . The method of  claim 1 , wherein the ratio of the opioid agonist to CYP2D6 inhibitor is about 1:0.1 to 1 (wt:wt). 
     
     
         14 . The method of  claim 1 , wherein the ratio of the opioid agonist to CYP2D6 inhibitor is about 0.1-1:1 (wt:wt). 
     
     
         15 . The method of  claim 1 , wherein the ratio of the opioid agonist to NMDA antagonist to CYP2D6 inhibitor is 1:1:0.1-1 (wt:wt:wt). 
     
     
         16 . The method of  claim 1 , wherein the ratio of the opioid agonist to NMDA antagonist to CYP2D6 inhibitor is about 1:1:1 (wt:wt:wt). 
     
     
         17 - 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the pharmaceutical composition is a dosage form. 
     
     
         20 . The method of  claim 19 , wherein said dosage form is an oral dosage form. 
     
     
         21 - 24 . (canceled) 
     
     
         25 . The method of  claim 2 , wherein the amount of the opioid agonist is less than when the opioid agonist is administered without one or more of the NMDA antagonist and the CYP2D6 inhibitor. 
     
     
         26 . A method of or increasing sleep in a subject with restless leg syndrome, the method comprising administering to the subject a pharmaceutical composition or a pharmaceutical dosage form comprising a NMDA antagonist; a CYP2D6 inhibitor; and an opioid agonist. 
     
     
         27 - 32 . (canceled)