Methods of inducing anesthesia

Abstract

The present invention provides methods for determining the selectivity of an anesthetic for an anesthetic-sensitive receptor by determining the molar water solubility of the anesthetic. The invention further provides methods for modulating the selectivity of an anesthetic for an anesthetic-sensitive receptor by altering or modifying the anesthetic to have higher or lower water solubility. The invention further provides methods of inducing anesthesia in a subject by administering via the respiratory pathways (e.g., via inhalational or pulmonary delivery) an effective amount of an anesthetic compound identified according to the present methods.

1 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula V: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9  and R 10  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
         wherein X is a halogen, the compound has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms of Formula V do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         2 . The method of  claim 1 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         3 . The method of  claim 1 , wherein X is F or Cl. 
     
     
         4 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 a) Cyclopentane, 5-chloro-1,1,2,2,3,3,4,4-octafluoro-(CAS#362014-70-8);   b) Cyclopentane, 1,1,2,2,3,4,4,5-octafluoro-(CAS#773-17-1);   c) Cyclopentane, 1,1,2,2,3,3,4,5-octafluoro-(CAS#828-35-3);   d) Cyclopentane, 1,1,2,3,3,4,5-heptafluoro-(CAS#3002-03-7);   e) Cyclopentane, 1,1,2,2,3,3,4,4-octafluoro-(CAS#149600-73-7);   f) Cyclopentane, 1,1,2,2,3,4,5-heptafluoro-(CAS#1765-23-7);   g) Cyclopentane, 1,1,2,3,4,5-hexafluoro-(CAS#699-38-7);   h) Cyclopentane, 1,1,2,2,3,3,4-heptafluoro-(CAS#15290-77-4);   i) Cyclopentane, 1,1,2,2,3,4-hexafluoro-(CAS#199989-36-1);   j) Cyclopentane, 1,1,2,2,3,3-hexafluoro-(CAS#123768-18-3); and   k) Cyclopentane, 1,1,2,2,3-pentafluoro-(CAS#1259529-57-1).   
     
     
         5 . The method of  claim 1 , wherein the compound is selected from the group consisting of:
 c) Cyclopentane, 1,1,2,2,3,3,4,5-octafluoro-(CAS#828-35-3);   e) Cyclopentane, 1,1,2,2,3,3,4,4-octafluoro-(CAS#149600-73-7); and   h) Cyclopentane, 1,1,2,2,3,3,4-heptafluoro-(CAS#15290-77-4).   
     
     
         6 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula I: 
       
         
           
           
               
               
           
         
         wherein: 
         n is 0-4, 
         R 1  is H; 
         R 2 , R 3 , R 4 , R 5  and R 6  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
         wherein X is a halogen, the compound having vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms in Formula I do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         7 . The method of  claim 6 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         8 . The method of  claim 6 , wherein X is F or Cl. 
     
     
         9 . The method of  claim 6 , wherein the compound is selected from the group consisting of:
 a) Methanol, 1-fluoro-1-[2,2,2-trifluoro-1-(trifluoromethyl)ethoxy]-(CAS #1351959-82-4);   b) 1-Butanol, 4,4,4-trifluoro-3,3-bis(trifluoromethyl)-(CAS#14115-49-2);   c) 1-Butanol, 1,1,2,2,3,3,4,4,4-nonafluoro-(CAS#3056-01-7);   d) 1-Butanol, 2,2,3,4,4,4-hexafluoro-3-(trifluoromethyl)-(CAS#782390-93-6);   e) 1-Butanol, 3,4,4,4-tetrafluoro-3-(trifluoromethyl)-(CAS#90999-87-4);   f) 1-Pentanol, 1,1,4,4,5,5,5-heptafluoro-(CAS#313503-66-1); and   g) 1-Pentanol, 1,1,2,2,3,3,4,4,5,5,5-undecafluoro-(CAS#57911-98-5).   
     
     
         10 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula II: 
       
         
           
           
               
               
           
         
         wherein: 
         n is 1-3, 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
         wherein X is a halogen, the compound having vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms in Formula II do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         11 . The method of  claim 10 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         12 . The method of  claim 10 , wherein X is F or Cl. 
     
     
         13 . The method of  claim 10 , wherein the compound is selected from the group consisting of:
 a) Ethane, 1,1,2-trifluoro-1,2-bis(trifluoromethoxy)-(CAS#362631-92-3);   b) Ethane, 1,1,1,2-tetrafluoro-2,2-bis(trifluoromethoxy)-(CAS#115395-39-6);   c) Ethane, 1-(difluoromethoxy)-1,1,2,2-tetrafluoro-2-(trifluoromethoxy)-(CAS#40891-98-3);   d) Ethane, 1,1,2,2-tetrafluoro-1,2-bis(trifluoromethoxy)-(CAS#378-11-0);   e) Ethane, 1,2-difluoro-1,2-bis(trifluoromethoxy)-(CAS#362631-95-6);   f) Ethane, 1,2-bis(trifluoromethoxy)-(CAS#1683-90-5);   g) Propane, 1,1,3,3-tetrafluoro-1,3-bis(trifluoromethoxy)-(CAS#870715-97-2);   h) Propane, 2,2-difluoro-1,3-bis(trifluoromethoxy)-(CAS#156833-18-0);   i) Propane, 1,1,1,3,3-pentafluoro-3-methoxy-2-(trifluoromethoxy)-(CAS#133640-19-4;   j) Propane, 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxymethoxy)-(CAS#124992-92-3); and   k) Propane, 1,1,1,2,3,3-hexafluoro-3-methoxy-2-(trifluoromethoxy)-(CAS#104159-55-9).   
     
     
         14 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula III: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
 wherein X is a halogen, the compound has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms of Formula III do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
 
     
     
         15 . The method of  claim 14 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         16 . The method of  claim 14 , wherein X is F or Cl. 
     
     
         17 . The method of  claim 14 , wherein the compound is selected from the group consisting of
 a) 1,4-Dioxane, 2,2,3,3,5,6-hexafluoro-(CAS#362631-99-0);   b) 1,4-Dioxane, 2,3-dichloro-2,3,5,5,6,6-hexafluoro-(CAS#135871-00-0);   c) 1,4-Dioxane, 2,3-dichloro-2,3,5,5,6,6-hexafluoro-, trans-(9CI) (CAS#56625-45-7);   d) 1,4-Dioxane, 2,3-dichloro-2,3,5,5,6,6-hexafluoro-, cis-(9CI) (CAS#56625-44-6);   e) 1,4-Dioxane, 2,2,3,5,6,6-hexafluoro-(CAS#56269-26-2);   f) 1,4-Dioxane, 2,2,3,5,5,6-hexafluoro-(CAS#56269-25-1);   g) 1,4-Dioxane, 2,2,3,3,5,6-hexafluoro-, trans-(9CI) (CAS#34206-83-2);   h) 1,4-Dioxane, 2,2,3,5,5,6-hexafluoro-, cis-(9CI) (CAS#34181-52-7);   i) p-Dioxane, 2,2,3,5,5,6-hexafluoro-, trans-(8CI) (CAS#34181-51-6);   j) 1,4-Dioxane, 2,2,3,5,6,6-hexafluoro-, cis-(9CI) (CAS#34181-50-5);   k) p-Dioxane, 2,2,3,5,6,6-hexafluoro-, trans-(8C1) (CAS#34181-49-2);   l) 1,4-Dioxane, 2,2,3,3,5,6-hexafluoro-, (5R,6S)-rel-(CAS#34181-48-1);   m) 1,4-Dioxane, 2,2,3,3,5,5,6-heptafluoro-(CAS#34118-18-8); and   n) 1,4-Dioxane, 2,2,3,3,5,5,6,6-octafluoro-(CAS#32981-22-9).   
     
     
         18 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula IV: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3 , R 4 , R 5  and R 6  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
         wherein X is a halogen, the compound has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms of Formula IV do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         19 . The method of  claim 18 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         20 . The method of  claim 18 , wherein X is F or Cl. 
     
     
         21 . The method of  claim 18 , wherein the compound is selected from the group consisting of:
 a) 1,3-Dioxolane, 2,4,4,5-tetrafluoro-5-(trifluoromethyl)-(CAS#344303-08-8);   b) 1,3-Dioxolane, 2-chloro-4,4,5-trifluoro-5-(trifluoromethyl)-(CAS#344303-05-5);   c) 1,3-Dioxolane, 4,4,5,5-tetrafluoro-2-(trifluoromethyl)-(CAS#269716-57-6);   d) 1,3-Dioxolane, 4-chloro-2,2,4-trifluoro-5-(trifluoromethyl)-(CAS#238754-29-5);   e) 1,3-Dioxolane, 4,5-dichloro-2,2,4,5-tetrafluoro-, trans-(9CI) (CAS #162970-78-7);   f) 1,3-Dioxolane, 4,5-dichloro-2,2,4,5-tetrafluoro-, cis-(9CI) (CAS#162970-76-5);   g) 1,3-Dioxolane, 4-chloro-2,2,4,5,5-pentafluoro-(CAS#139139-68-7);   h) 1,3-Dioxolane, 4,5-dichloro-2,2,4,5-tetrafluoro-(CAS#87075-00-1);   i) 1,3-Dioxolane, 2,4,4,5-tetrafluoro-5-(trifluoromethyl)-, trans-(9CI) (CAS#85036-66-4);   j) 1,3-Dioxolane, 2,4,4,5-tetrafluoro-5-(trifluoromethyl)-, cis-(9CI) (CAS#85036-65-3);   k) 1,3-Dioxolane, 2-chloro-4,4,5-trifluoro-5-(trifluoromethyl)-, trans-(9CI) (CAS#85036-60-8);   l) 1,3-Dioxolane, 2-chloro-4,4,5-trifluoro-5-(trifluoromethyl)-, cis-(9CI) (CAS#85036-57-3);   m) 1,3-Dioxolane, 2,2-dichloro-4,4,5,5-tetrafluoro-(CAS#85036-55-1);   n) 1,3-Dioxolane, 4,4,5-trifluoro-5-(trifluoromethyl)-(CAS#76492-99-4);   o) 1,3-Dioxolane, 4,4-difluoro-2,2-bis(trifluoromethyl)-(CAS#64499-86-1);   p) 1,3-Dioxolane, 4,5-difluoro-2,2-bis(trifluoromethyl)-, cis-(9CI) (CAS#64499-85-0);   q) 1,3-Dioxolane, 4,5-difluoro-2,2-bis(trifluoromethyl)-, trans-(9CI) (CAS#64499-66-7);   r) 1,3-Dioxolane, 4,4,5-trifluoro-2,2-bis(trifluoromethyl)-(CAS#64499-65-6);   s) 1,3-Dioxolane, 2,4,4,5,5-pentafluoro-2-(trifluoromethyl)-(CAS#55135-01-8);   t) 1,3-Dioxolane, 2,2,4,4,5,5-hexafluoro-(CAS#21297-65-4); and   u) 1,3-Dioxolane, 2,2,4,4,5-pentafluoro-5-(trifluoromethyl)-(CAS#19701-22-5).   
     
     
         22 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of 1,1,2,2,3,3,4,4-octafluoro-cyclohexane (CAS#830-15-9), thereby inducing anesthesia in the subject. 
     
     
         23 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula VI: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7  and R 8  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X and C 2 X 5 ; and 
         wherein X is a halogen, the compound has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms of Formula VI do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         24 . The method of  claim 23 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         25 . The method of  claim 23 , wherein X is F or Cl. 
     
     
         26 . The method of  claim 23 , wherein the compound is selected from the group consisting of:
 a) Furan, 2,3,4,4-tetrafluorotetrahydro-2,3-bis(trifluoromethyl)-(CAS#634191-25-6);   b) Furan, 2,2,3,3,4,4,5-heptafluorotetrahydro-5-(trifluoromethyl)-(CAS#377-83-3);   c) Furan, 2,2,3,3,4,5,5-heptafluorotetrahydro-4-(trifluoromethyl)-(CAS#374-53-8);   d) Furan, 2,2,3,4,5-pentafluorotetrahydro-5-(trifluoromethyl)-, (2a,3β,4a)-(9CI) (CAS#133618-53-8);   e) Furan, 2,2,3,4,5-pentafluorotetrahydro-5-(trifluoromethyl)-, (2a,3a,4B)-(CAS#133618-52-7);   f) Furan, 2,2,3,4,5-pentafluorotetrahydro-5-(trifluoromethyl)-, (2α,3β,4α)-(9CI) (CAS#133618-53-8);   g) Furan, 2,2,3,4,5-pentafluorotetrahydro-5-(trifluoromethyl)-, (2α,3α,4β)-(9CI) (CAS#133618-52-7);   h) Furan, 2,2,3,3,5,5-hexafluorotetrahydro-4-(trifluoromethyl)-(CAS#61340-70-3);   i) Furan, 2,3-difluorotetrahydro-2,3-bis(trifluoromethyl)-(CAS#634191-26-7);   j) Furan, 2-chloro-2,3,3,4,4,5,5-heptafluorotetrahydro-(CAS#1026470-51-8);   k) Furan, 2,2,3,3,4,4,5-heptafluorotetrahydro-5-methyl-(CAS#179017-83-5);   l) Furan, 2,2,3,3,4,5-hexafluorotetrahydro-5-(trifluoromethyl)-, trans-(9CI) (CAS#133618-59-4); and   m) Furan, 2,2,3,3,4,5-hexafluorotetrahydro-5-(trifluoromethyl)-, cis-(9CI) (CAS#133618-49-2).   
     
     
         27 . A method of inducing anesthesia in a subject, comprising administering to the subject via the respiratory system an effective amount of a compound or a mixture of compounds of Formula VII: 
       
         
           
           
               
               
           
         
         wherein: 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9  and R 10  independently are selected from H, X, CX 3 , CHX 2 , CH 2 X, and C 2 X 5 ; and 
         wherein X is a halogen, the compound has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms of Formula VII do not exceed the number of carbon atoms, thereby inducing anesthesia in the subject. 
       
     
     
         28 . The method of  claim 27 , wherein X is a halogen selected from the group consisting of F, Cl, Br and I. 
     
     
         29 . The method of  claim 27 , wherein X is F or Cl. 
     
     
         30 . The method of  claim 27 , wherein the compound is selected from the group consisting of:
 a) 2H-Pyran, 2,2,3,3,4,5,5,6,6-nonafluorotetrahydro-4-(CAS #71546-79-7);   b) 2H-Pyran, 2,2,3,3,4,4,5,5,6-nonafluorotetrahydro-6-(trifluoromethyl)-(CAS#356-47-8);   c) 2H-Pyran, 2,2,3,3,4,4,5,6,6-nonafluorotetrahydro-5-(trifluoromethyl)-(CAS#61340-74-7);   d) 2H-Pyran, 2,2,6,6-tetrafluorotetrahydro-4-(trifluoromethyl)-(CAS#657-48-7);   e) 2H-Pyran, 2,2,3,3,4,4,5,5,6-nonafluorotetrahydro-6-methyl-(CAS#874634-55-6);   f) Perfluorotetrahydropyran (CAS#355-79-3);   g) 2H-Pyran, 2,2,3,3,4,5,5,6-octafluorotetrahydro-, (4R,6S)-rel-(CAS#362631-93-4); and   h) 2H-Pyran, 2,2,3,3,4,4,5,5,6-nonafluorotetrahydro-(CAS#65601-69-6).   
     
     
         31 . The method of  claim 6 , wherein the compound has a molar water solubility of less than about 1.1 mM and greater than about 0.016 mM. 
     
     
         32 . The method of  claim 6 , wherein the compound potentiates GABA A  receptors, but does not inhibit NMDA receptors. 
     
     
         33 . The method of  claim 6 , wherein the subject is a mammal. 
     
     
         34 . The method of  claim 6 , wherein the subject is a human. 
     
     
         35 . A composition comprising a compound or a mixture of compounds used in the methods of  claim 6 , wherein the composition is formulated for inhalational or pulmonary delivery of the compound or mixture of compounds. 
     
     
         36 . A method of selecting an anesthetic that preferentially activates or potentiates GABA A  receptors without inhibiting NMDA receptors, comprising:
 a) determining the molar water solubility of the anesthetic; and   b) selecting an anesthetic with a molar water solubility below about 1.1 mM, wherein the anesthetic selectively potentiates GABA A  receptors and does not inhibit NMDA receptors, whereby an anesthetic that preferentially activates or potentiates GABA A  receptors without inhibiting NMDA receptors is selected.   
     
     
         37 . A method of selecting an anesthetic that both potentiates GABA A  receptors and inhibits NMDA receptors, comprising:
 a) determining the molar water solubility of the anesthetic; and   b) selecting an anesthetic with a molar water solubility above about 1.1 mM, wherein the anesthetic both potentiates GABA A  receptors and inhibits NMDA receptors, whereby an anesthetic that both potentiates GABA A  receptors and inhibits NMDA receptors is selected.   
     
     
         38 . The method of  claim 36 , wherein the anesthetic is an inhalational anesthetic. 
     
     
         39 . The method of  claim 36 , wherein the anesthetic is selected from the group consisting of halogenated alcohols, halogenated diethers, halogenated dioxanes, halogenated dioxolanes, halogenated cyclopentanes, halogenated cyclohexanes, halogenated tetrahydrofurans and halogenated tetrahydropyrans, wherein the anesthetic has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms do not exceed the number of carbon atoms. 
     
     
         40 . The method of  claim 36 , wherein the anesthetic is selected from the compounds administered in the methods of any one of  claims 6  to  32 . 
     
     
         41 . The method of  claim 36 , wherein the anesthetic is selected from the group consisting of nonane, midazolam, diazepam, undecanol, etomidate, 1,2-dichlorohexafluorocyclobutane, and analogs thereof. 
     
     
         42 . The method of  claim 37 , wherein the anesthetic is selected from the group consisting of sevoflurane, propofol, ketamine, isoflurane, enflurane, dizocilpine, desflurane, halothane, cyclopropane, chloroform, 2,6-dimethylphenol, methoxyflurane, diethyl ether, nitrous oxide, ethanol, and analogs thereof. 
     
     
         43 . A method of determining the specificity of an anesthetic for an anesthetic-sensitive receptor comprising determining whether the molar water solubility of the anesthetic is above or below a predetermined solubility threshold concentration for an anesthetic-sensitive receptor,
 wherein an anesthetic with a molar water solubility below about 1.2 mM does not inhibit Na v  channels, but can inhibit NMDA receptors, potentiate two-pore domain potassium channels (K 2P ), potentiate glycine receptors and potentiate GABA A  receptors;   wherein an anesthetic with a molar water solubility below about 1.1 mM does not inhibit Na v  channels or inhibit NMDA receptors, but can potentiate two-pore domain potassium channels (K 2P ), potentiate glycine receptors and potentiate GABA A  receptors;   wherein an anesthetic with a molar water solubility below about 0.26 mM does not inhibit Na v  channels, inhibit NMDA receptors or potentiate two-pore domain potassium channel (K 2P ) currents, but can potentiate glycine receptors and potentiate GABA A  receptors; and   wherein an anesthetic with a molar water solubility below about 68 μM does not inhibit Na v  channels, inhibit NMDA receptors, potentiate two-pore domain potassium channel (K 2P ) currents, or potentiate GABA A  receptors but can potentiate glycine receptors; thereby determining the specificity of an anesthetic for an anesthetic-sensitive receptor.   
     
     
         44 . The method of  claim 43 , wherein the anesthetic is selected from the compounds administered in the methods of  claim 6 . 
     
     
         45 . A method of modulating the specificity of an anesthetic for an anesthetic-sensitive receptor comprising adjusting the molar water solubility of the anesthetic to be above a predetermined water solubility threshold concentration for an anesthetic-sensitive receptor that the anesthetic can modulate or adjusting the molar water solubility of the anesthetic to be below a predetermined molar water solubility threshold concentration for an anesthetic-sensitive receptor that the anesthetic cannot modulate;
 wherein an anesthetic with a molar water solubility below about 1.2 mM does not inhibit Na v  channels, but can inhibit NMDA receptors, potentiate two-pore domain potassium channels (K 2P ), potentiate glycine receptors and potentiate GABA A  receptors;   wherein an anesthetic with a molar water solubility below about 1.1 mM does not inhibit Na v  channels or inhibit NMDA receptors, but can potentiate two-pore domain potassium channels (K 2P ), potentiate glycine receptors and potentiate GABA A  receptors;   wherein an anesthetic with a molar water solubility below about 0.26 mM does not inhibit Na v  channels, inhibit NMDA receptors or potentiate two-pore domain potassium channel (K 2P ) currents, but can potentiate glycine receptors and potentiate GABA A  receptors; and   wherein an anesthetic with a molar water solubility below about 68 μM does not inhibit Na v  channels, inhibit NMDA receptors, potentiate two-pore domain potassium channel (K 2P ) currents, or potentiate GABA A  receptors but can potentiate glycine receptors; thereby determining the specificity of an anesthetic for an anesthetic-sensitive receptor.   
     
     
         46 . The method  claim 45 , wherein the anesthetic is an inhalational anesthetic. 
     
     
         47 . The method of  claim 45 , wherein the anesthetic is selected from the group consisting of halogenated alcohols, halogenated diethers, halogenated dioxanes, halogenated dioxolanes, halogenated cyclopentanes, halogenated cyclohexanes, halogenated tetrahydrofurans and halogenated tetrahydropyrans, wherein the anesthetic has a vapor pressure of at least 0.1 atmospheres (76 mmHg) at 25° C., and the number of hydrogen atoms do not exceed the number of carbon atoms. 
     
     
         48 . The method of  claim 45 , wherein the anesthetic is selected from the compounds administered in the methods of any one of  claims 6  to  32 . 
     
     
         49 . The method of  claim 45 , wherein the anesthetic is selected from the group consisting of nonane, midazolam, diazepam, undecanol, etomidate, 1,2-dichlorohexafluorocyclobutane, and analogs thereof. 
     
     
         50 . The method of  claim 45 , wherein the anesthetic is selected from the group consisting of sevoflurane, propofol, ketamine, isoflurane, enflurane, dizocilpine, desflurane, halothane, cyclopropane, chloroform, 2,6-dimethylphenol, methoxyflurane, diethyl ether, nitrous oxide, ethanol, and analogs thereof. 
     
     
         51 . The method of  claim 45 , wherein the anesthetic is adjusted to have a molar water solubility of less than about 1.1 mM and potentiates GABA A  receptors but does not inhibit NMDA receptors. 
     
     
         52 . The method of  claim 45 , wherein the anesthetic is adjusted to have a molar water solubility of greater than about 1.1 mM and both potentiates GABA A  receptors and inhibits NMDA receptors. 
     
     
         53 . The method of  claim 45 , wherein the anesthetic is an analog of an inhalational anesthetic.