Deuterated caffeine and uses thereof

Abstract

Provided herein are compositions (e.g., pharmaceutical compositions, nutraceutical compositions, foods, beverages, cosmetic compositions, diet supplements) comprising deuterated caffeine. The provided compositions may be useful for treating and/or preventing various diseases and conditions, such as obesity, causing weight loss, increasing metabolic rate, reducing appetite, increasing energy expenditure, increasing urine output, increasing sodium excretion, reducing edema, a pain disorder, apnea, hypotension, an encephalopathy, a neurological or psychiatric disorder, and an inflammatory disorder.

1 - 139 . (canceled) 
     
     
         140 . A pharmaceutical composition comprising a compound of Formula (I): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; 
         wherein each Y is independently hydrogen or deuterium; and 9 or 10 instances of Y are deuterium. 
       
     
     
         141 . The pharmaceutical composition of  claim 140 , wherein the compound of Formula (I) is a pharmaceutically acceptable salt. 
     
     
         142 . The pharmaceutical composition of  claim 141 , wherein the pharmaceutically acceptable salt is a citrate salt. 
     
     
         143 . The pharmaceutical composition of  claim 140 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         144 . The pharmaceutical composition of  claim 140 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         145 . The pharmaceutical composition of  claim 140 , wherein the composition is suitable for oral administration, parenteral administration, topical administration, inhalation, buccal administration, or for delivery to the lungs. 
     
     
         146 . The pharmaceutical composition of  claim 145 , wherein the parenteral administration is intravenous administration. 
     
     
         147 . The pharmaceutical composition of  claim 140  comprising about 1 mg/ml to about 100 mg/ml of the compound of Formula (I), or a pharmaceutically acceptable salt thereof. 
     
     
         148 . The pharmaceutical composition of  claim 145 , wherein the composition is a solid dose form suitable for oral administration. 
     
     
         149 . The pharmaceutical composition of  claim 148 , comprising about 1 mg to about 1000 mg of the compound of Formula (I), or a pharmaceutically acceptable salt thereof. 
     
     
         150 . The pharmaceutical composition of  claim 140  further comprising an additional active agent. 
     
     
         151 . The pharmaceutical composition of  claim 149 , wherein the additional active agent is ergotamine, an anti-inflammatory agent, a steroid, a barbiturate, an opioid analgesic, or a combination thereof. 
     
     
         152 . The pharmaceutical composition of  claim 151 , wherein the anti-inflammatory agent is a cyclooxygenase-3 (COX-3) inhibitor, a non-steroidal anti-inflammatory drug (NSAID), or a cyclooxygenase-2 (COX-2) inhibitor. 
     
     
         153 . The pharmaceutical composition of  claim 152 , wherein the NSAID is ibuprofen, naproxen, sulindac, ketoprofen, tolmetin, etodolac, fenoprofen, diclofenac, flurbiprofen, piroxicam, ketorolac, indomethacin, nabumetone, oxaprozin, mefanamic acid, or diflunisal. 
     
     
         154 . The pharmaceutical composition of  claim 151 , wherein the opioid analgesic is codeine, fentanyl, hydrocodone, hydromorphone, meperidine, methadone, morphine, or oxycodone. 
     
     
         155 . The pharmaceutical composition of  claim 151 , wherein the barbiturate is secobarbital, mephobarbital, pentobarbital, butabarbital, phenobarbital, or amobarbital. 
     
     
         156 . The pharmaceutical composition of  claim 151 , wherein the COX-2 inhibitor is celecoxib, valdecoxib, rofecoxib, or etoricoxib. 
     
     
         157 . The pharmaceutical composition of  claim 151 , wherein the COX-3 inhibitor is acetaminophen, phenacetin, antipyrine, or dipyrone. 
     
     
         158 . The pharmaceutical composition of  claim 140 , wherein the maximum plasma concentration (C max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is substantially similar to or lower than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         159 . The pharmaceutical composition of  claim 158 , wherein the maximum plasma concentration (C max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 25% lower than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         160 . The pharmaceutical composition of  claim 158 , wherein the maximum plasma concentration (C max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 50% lower than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         161 . The pharmaceutical composition of  claim 140 , wherein the time to maximum plasma concentration (T max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 10% longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         162 . The pharmaceutical composition of  claim 140 , wherein the time to maximum plasma concentration (T max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 25% longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         163 . The pharmaceutical composition of  claim 140 , wherein the time to maximum plasma concentration (T max ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 50% longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         164 . The pharmaceutical composition of  claim 140 , wherein the maximum concentration (C max ) of the compound of Formula (I) in the central nervous system of a subject after administration of the composition to the subject is substantially similar to or lower than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         165 . The pharmaceutical composition of  claim 164 , wherein the maximum concentration (C max ) of the compound of Formula (I) in the central nervous system of a subject after administration of the composition to the subject is at least 10% lower than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         166 . The pharmaceutical composition of  claim 140 , wherein the time to maximum concentration (T max ) of the compound of Formula (I) in the central nervous system of a subject after administration of the composition to the subject is at least 10% longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         167 . The pharmaceutical composition of  claim 140 , wherein the time to maximum concentration (T max ) of the compound of Formula (I) in the central nervous system of a subject after administration of the composition to the subject is at least 25% longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         168 . The pharmaceutical composition of  claim 140 , wherein the plasma half-life (t 1/2 ) of the compound of Formula (I) in a subject after administration of the composition to the subject is longer than that of non-isotopically enriched caffeine at an equivalent dose. 
     
     
         169 . The pharmaceutical composition of  claim 168 , wherein the plasma half-life (t 1/2 ) of the compound of Formula (I) in a subject after administration of the composition to the subject is at least 5%, 10%, 25%, 50%, 100%, 200%, 300%, or 400% longer than that of non-isotopically enriched caffeine at an equivalent dose.