What is claimed is:
1. A handsaw comprising:
a handle including:
a slit defined in a front end of the handle and parallel to a left and a right side of the handle;
an opening defined in a rear end of the handle for holding;
a pivot hole defined in the front end of the handle, transversely extending through the handle and communicating with the slit in the handle; and
a positioning hole defined between the opening and the pivot hole, transversely extending through the handle and communicating with the slit in the handle;
a saw blade selectively pivotally connected to the handle and partially received in the slit in the handle, the saw blade having a front and rear end and including:
multiple indents defined in the rear end of the saw blade and corresponding to the positioning hole in the handle;
multiple protrusions formed between adjacent indents; and
a through hole defined in the saw blade and corresponding to the pivot hole in the handle; and
a position device mounted in the handle to hold the saw blade in place, the position device including:
a pivot pin mounted in the pivot hole in the handle to pivotally mount the saw blade in the handle; and
a locking pin movably mounted in the positioning hole to engage an indent in the saw blade, the locking pin extending through the handle after penetrating a spring and having a locking member attached to a free end of the locking pin to prevent the locking pin from detaching from the handle.
2. The handsaw as claimed in claim 1, wherein:
the handle comprises:
a first enlarged countersunk hole defined in a left side of the handle and communicating with the pivot hole of the handle; and
a first polygonal recess defined in the handle between the first enlarged countersunk hole and the slit, the first polygonal recess communicating with the first enlarged countersunk hole and having an area smaller than that of the first enlarged countersunk hole; and
the pivot pin comprises:
a head received in the first enlarged countersunk hole in the handle;
a block extending from the head and received in the first polygonal recess to prevent the pivot pin from rotating in the pivot hole, the block being polygonal and corresponding to the first polygonal recess; and
a rod extending from the block, the rod received in the pivot hole and extending through the handle, the rod having a threaded free end and a nut screwed onto the free end of the rod to prevent the pivot pin from detaching from the handle.
3. The handsaw as claimed in claim 1, wherein:
the handle comprises:
a second enlarged countersunk hole defined in the left side of the handle and communicating with the positioning hole;
a second polygonal recess defined in the handle between the second enlarged countersunk hole and the slit, the second polygonal recess communicating with the second enlarged countersunk hole and having an area smaller than that of the second enlarged countersunk hole; and
a third enlarged countersunk hole defined in a right side of the handle and communicating with the positioning hole in the handle to receive the locking element in the third enlarged countersunk hole;
the locking pin comprises:
a button received in the second enlarged countersunk hole in the handle;
a position block extending from the button and received in the second polygonal recess, the position block being polygonal and engaged to the second polygonal recess to prevent the locking pin from rotated in the positioning hole;
a channel defined in the position block to allow the protrusion of the saw blade to pass through when the button is pressed down;
a position pin extending from the position block and received in the positioning hole to engage an indent in the saw blade, the position pin having a first end connecting to the position block and a second end extending to the third enlarged countersunk hole for the locking element attached to the position pin; and
a guiding portion defined in the first end of the position pin and tapered off to the position block.
4. The handsaw as claimed in claim 2, wherein:
the handle comprises:
a second enlarged countersunk hole defined in the left side of the handle and communicating with the positioning hole;
a second polygonal recess defined in the handle between the second enlarged countersunk hole and the slit, the second polygonal recess communicating with the second enlarged countersunk hole and having an area smaller than that of the second enlarged countersunk hole; and
a third enlarged countersunk hole defined in a right side of the handle and communicating with the positioning hole in the handle to receive the locking element in the third enlarged countersunk hole;
the locking pin comprises:
a button received in the second enlarged countersunk hole in the handle;
a position block extending from the button and received in the second polygonal recess, the position block being polygonal and engaged with the second polygonal recess to prevent the locking pin from rotating in the positioning hole;
a channel defined in the position block to allow the protrusion of the saw blade to pass through when the button is pressed down;
a position pin extending from the position block and received in the positioning hole to engage an indent in the saw blade, the position pin having a first end connecting to the position block and a second end extending to the third enlarged countersunk hole for the locking element to be attached to the position pin; and
a guiding portion defined in the first end of the position pin and tapered off to the position block.
5. The handsaw as claimed in claim 1, wherein the locking element is an E-shaped ring.
6. The handsaw as claimed in claim 3, wherein the locking element is an E-shaped ring.
7. The handsaw as claimed in claim 4, wherein the locking element is an E-shaped ring.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound having structural Formula I
or a pharmaceutically acceptable salt thereof; wherein:
R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 are independently selected from the group consisting of hydrogen and deuterium; and
at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 is deuterium.
2. The compound as recited in claim 1, wherein said compound is substantially a single enantiomer, a mixture of about 90% or more by weight of the (\u2212)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (\u2212)-enantiomer, substantially an individual diastereomer, or a mixture of about 90% or more by weight of an individual diastereomer and about 10% or less by weight of any other diastereomer.
3. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 98%.
4. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 90%.
5. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 50%.
6. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 20%.
7. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 10%.
8. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 5%.
9. The compound as recited in claim 1, wherein at least one of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, and R16 independently has deuterium enrichment of no less than about 1%.
10. The compound as recited in claim 1, wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
11. The compound as recited in claim 10, wherein said compound is substantially a single enantiomer, a mixture of about 90% or more by weight of the (\u2212)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (\u2212)-enantiomer, substantially an individual diastereomer, or a mixture of about 90% or more by weight of an individual diastereomer and about 10% or less by weight of any other diastereomer.
12. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 98%.
13. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 90%.
14. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 50%.
15. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 20%.
16. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 10%.
17. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 5%.
18. The compound as recited in claim 10, wherein each of said positions represented as D have deuterium enrichment of at least 1%.
19. The compound as recited in claim 1, wherein the compound is selected from the group consisting of:
20. The compound as recited in claim 19, wherein said compound is substantially a single enantiomer, a mixture of about 90% or more by weight of the (\u2212)-enantiomer and about 10% or less by weight of the (+)-enantiomer, a mixture of about 90% or more by weight of the (+)-enantiomer and about 10% or less by weight of the (\u2212)-enantiomer, substantially an individual diastereomer, or a mixture of about 90% or more by weight of an individual diastereomer and about 10% or less by weight of any other diastereomer.
21. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 98%.
22. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 90%.
23. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 50%.
24. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 20%.
25. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 10%.
26. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 5%.
27. The compound as recited in claim 19, wherein each of said positions represented as D have deuterium enrichment of at least 1%.
28. A pharmaceutical composition comprising the compound as recited in claim 1 and one or more pharmaceutically acceptable carriers.
29. The pharmaceutical composition as recited in claim 28, further comprising one or more release-controlling excipients.
30. The pharmaceutical composition as recited in claim 28, further comprising one or more non-release controlling excipients.
31. The pharmaceutical composition as recited in claim 28, wherein the composition is suitable for oral, parenteral, or intravenous infusion administration.
32. The pharmaceutical composition as recited in claim 31, wherein the oral dosage form is a tablet or capsule.
33. The pharmaceutical composition as recited in claim 31, wherein the compound is administered in a dose of about 0.5 milligram to about 1,000 milligram.
34. The pharmaceutical composition as recited in claim 28, further comprising another therapeutic agent.
35. The pharmaceutical composition as recited in claim 34, wherein the therapeutic agent is selected from the group consisting of NMDA receptor modulators, opioids, anesthetics, benzodiazepines, peripherally acting muscle relaxants, endothelin converting enzyme (ECE) inhibitors, thromboxane enzyme antagonists, potassium channel openers, thrombin inhibitors, growth factor inhibitors, platelet activating factor (PAF) antagonists, anti-platelet agents, Factor VIIa Inhibitors, Factor Xa Inhibitors, renin inhibitors, neutral endopeptidase (NEP) inhibitors, vasopepsidase inhibitors, HMG CoA reductase inhibitors, squalene synthetase inhibitors, fibrates, bile acid sequestrants, anti-atherosclerotic agents, MTP Inhibitors, calcium channel blockers, potassium channel activators, alpha-PDE5 agents, beta-PDE5 agents, antiarrhythmic agents, diuretics, anti-diabetic agents, PPAR-gamma agonists, mineralocorticoid enzyme antagonists, aP2 inhibitors, protein tyrosine kinase inhibitors, antiinflammatories, antiproliferatives, chemotherapeutic agents, immunosuppressants, anticancer agents, cytotoxic agents, antimetabolites, farnesyl-protein transferase inhibitors, hormonal agents, microtubule-disruptor agents, microtubule-stablizing agents, topoisomerase inhibitors, prenyl-protein transferase inhibitors, cyclosporins, TNF-alpha inhibitors, cyclooxygenase-2 (COX-2) inhibitors, gold compounds, and platinum coordination complexes.
36. The pharmaceutical composition as recited in claim 35, wherein the therapeutic agent is a NMDA receptor modulator.
37. The pharmaceutical composition as recited in claim 36, wherein the NMDA receptor modulator is selected from the group consisting of phencyclidine (PCP), amantadine, ibogaine, memantine, nitrous oxide, and dextromethorphan.
38. The pharmaceutical composition as recited in claim 35, wherein the therapeutic agent is an opioid.
39. The pharmaceutical composition as recited in claim 38, wherein the opioid is selected from the group consisting of morphine, codeine, thebain, diacetylmorphine, oxycodone, hydrocodone, hydromorphone, oxymorphone, nicomorphine, fentanyl, \u03b1-methylfentanyl, alfentanil, sufentanil, remifentanyl, carfentanyl, ohmefentanyl, pethidine, ketobemidone, propoxyphene, dextropropoxyphene, methadone, loperamide, pentazocine, buprenorphine, etorphine, butorphanol, nalbufine, levorphanol, naloxone, naltrexone, and tramadol.
40. The pharmaceutical composition as recited in claim 35, wherein the therapeutic agent is an anesthetic.
41. The pharmaceutical composition as recited in claim 40, wherein the anesthetic is selected from the group consisting of diethyl ether, vinyl ether, halothane, chloroform, methoxyflurane, enflurane, trichioroethylene, isoflurane, desfiurane, sevoflurane, methohexital, hexobarbital, thiopental, narcobarbital, fentanyl, alfentanil, sufentanil, phenoperidine, anileridine, remifentanil, droperidol, ketamine, propanidid, alfaxalone, etomidate, propofol, hydroxybutyric acid, nitrous oxide, esketamine, metabutethamine, procaine, tetracaine, chioroprocaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, butanilicaine, cinchocaine, etidocaine, articaine, ropivacaine, levobupivacaine, cocaine, ethyl chloride, dyclonine, phenol, and capsaicin.
42. The pharmaceutical composition as recited in claim 35, wherein the therapeutic agent is a benzodiazepine.
43. The pharmaceutical composition as recited in claim 42, wherein the benzodiazepine is selected from the group consisting of alprazolam, bromazepam, clonazepam, diazepam, estazolam, flunitrazepam, lorazepam, midazolam, nitrazepam, oxazepam, triazolam, temazepam, and chlordiazepoxide.
44. The pharmaceutical composition as recited in claim 35, wherein the therapeutic agent is a peripherally acting muscle relaxant.
45. The pharmaceutical composition as recited in claim 44, wherein the peripherally acting muscle relaxant is selected from the group consisting of alcuronium, dimethyltubocurarine, tubocurarine, suxamethonium, atracurium, cisatracurium, doxacurium chloride, fazadinium bromide, gallamine, hexafluronium, mivacurium chloride, pancuronium, pipecuronium bromide, rocuronium bromide, vecuronium, and botulinum toxin.
46. A pharmaceutical composition comprising the compound as recited in claim 19, and one or more pharmaceutically acceptable carriers.
47. The pharmaceutical composition as recited in claim 46, further comprising one or more release-controlling excipients.
48. The pharmaceutical composition as recited in claim 46, further comprising one or more non-release controlling excipients.
49. The pharmaceutical composition as recited in claim 46, wherein the composition is suitable for oral, parenteral or intravenous infusion administration.
50. The pharmaceutical composition as recited in claim 49, wherein the oral dosage form is a tablet or capsule.
51. The pharmaceutical composition as recited in claim 49, wherein the compound is administered in a dose of about 0.5 milligrams to about 1,000 milligrams.
52. The pharmaceutical composition as recited in claim 46, further comprising another therapeutic agent.
53. The pharmaceutical composition as recited in claim 52, wherein the therapeutic agent is selected from the group consisting of NMDA receptor modulators, opioids, anesthetics, benzodiazepines, peripherally acting muscle relaxants, endothelin converting enzyme (ECE) inhibitors, thromboxane enzyme antagonists, potassium channel openers, thrombin inhibitors, growth factor inhibitors, platelet activating factor (PAF) antagonists, anti-platelet agents, Factor VIIa Inhibitors, Factor Xa Inhibitors, renin inhibitors, neutral endopeptidase (NEP) inhibitors, vasopepsidase inhibitors, HMG CoA reductase inhibitors, squalene synthetase inhibitors, fibrates, bile acid sequestrants, anti-atherosclerotic agents, MTP Inhibitors, calcium channel blockers, potassium channel activators, alpha-PDE5 agents, beta-PDE5 agents, antiarrhythmic agents, diuretics, anti-diabetic agents, PPAR-gamma agonists, mineralocorticoid enzyme antagonists, aP2 inhibitors, protein tyrosine kinase inhibitors, antiinflammatories, antiproliferatives, chemotherapeutic agents, immunosuppressants, anticancer agents, cytotoxic agents, antimetabolites, famesyl-protein transferase inhibitors, hormonal agents, microtubule-disruptor agents, microtubule-stablizing agents, topoisomerase inhibitors, prenyl-protein transferase inhibitors, cyclosporins, TNF-alpha inhibitors, cyclooxygenase-2 (COX-2) inhibitors, gold compounds, and platinum coordination complexes.
54. The pharmaceutical composition as recited in claim 53, wherein the therapeutic agent is a NMDA receptor modulator.
55. The pharmaceutical composition as recited in claim 54, wherein the NMDA receptor modulator is selected from the group consisting of phencyclidine (PCP), amantadine, ibogaine, memantine, nitrous oxide, and dextromethorphan.
56. The pharmaceutical composition as recited in claim 53, wherein the therapeutic agent is an opioid.
57. The pharmaceutical composition as recited in claim 56, wherein the opioid is selected from the group consisting of morphine, codeine, thebain, diacetylmorphine, oxycodone, hydrocodone, hydromorphone, oxymorphone, nicomorphine, fentanyl, \u03b1-methylfentanyl, alfentanil, sufentanil, remifentanyl, carfentanyl, ohmefentanyl, pethidine, ketobemidone, propoxyphene, dextropropoxyphene, methadone, loperamide, pentazocine, buprenorphine, etorphine, butorphanol, nalbufine, levorphanol, naloxone, naltrexone, and tramadol.
58. The pharmaceutical composition as recited in claim 53, wherein the therapeutic agent is an anesthetic.
59. The pharmaceutical composition as recited in claim 58, wherein the anesthetic is selected from the group consisting of diethyl ether, vinyl ether, halothane, chloroform, methoxyflurane, enflurane, trichloroethylene, isoflurane, desfiurane, sevoflurane, methohexital, hexobarbital, thiopental, narcobarbital, fentanyl, alfentanil, sufentanil, phenoperidine, anileridine, remifentanil, droperidol, ketamine, propanidid, alfaxalone, etomidate, propofol, hydroxybutyric acid, nitrous oxide, esketamine, metabutethamine, procaine, tetracaine, chloroprocaine, benzocaine, bupivacaine, lidocaine, mepivacaine, prilocaine, butanilicaine, cinchocaine, etidocaine, articaine, ropivacaine, levobupivacaine, cocaine, ethyl chloride, dyclonine, phenol, and capsaicin.
60. The pharmaceutical composition as recited in claim 53, wherein the therapeutic agent is a benzodiazepine.
61. The pharmaceutical composition as recited in claim 60, wherein the benzodiazepine is selected from the group consisting of alprazolam, bromazepam, clonazepam, diazepam, estazolam, flunitrazepam, lorazepam, midazolam, nitrazepam, oxazepam, triazolam, temazepam, and chlordiazepoxide.
62. The pharmaceutical composition as recited in claim 53, wherein the therapeutic agent is a peripherally acting muscle relaxant.
63. The pharmaceutical composition as recited in claim 62, wherein the peripherally acting muscle relaxant is selected from the group consisting of alcuronium, dimethyltubocurarine, tubocurarine, suxamethonium, atracurium, cisatracurium, doxacurium chloride, fazadinium bromide, gallamine, hexafluronium, mivacurium chloride, pancuronium, pipecuronium bromide, rocuronium bromide, vecuronium, and botulinum toxin.
64. A method for the treatment, prevention, or amelioration of one or more symptoms of a NMDA receptor-mediated disorder in a subject comprising administering a therapeutically effective amount of a compound as recited in claim 1.
65. The method as recited in claim 64, wherein the NMDA receptor-mediated disorder is selected from the group consisting of nociceptive pain, neuropathic pain, phantom limb pain, ischemic pain, stroke, sepsis, inflammation, opioid tolerance, Alzheimer’s disease, and bum.
66. The method as recited in claim 64, wherein the NMDA receptor-mediated disorder can be lessened, alleviated, or prevented by using an agent selected from the group consisting of an anesthetic, analgesic, entheogen, therapeutic cataleptic, and neuroprotectant.
67. The method as recited in claim 66, wherein the anesthetic promotes general anaesthesia.
68. The method as recited in claim 64, wherein the NMDA receptor-mediated disorder can be lessened, alleviated, or prevented by administering a NDMA receptor modulator.
69. The method as recited in claim 64, wherein said compound has at least one of the following properties:
a) decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b) increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c) decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d) increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e) an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
70. The method as recited in claim 64, wherein said compound has at least two of the following properties:
a) decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b) increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c) decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d) increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e) an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
71. The method as recited in claim 64, wherein the method affects a decreased metabolism of the compound per dosage unit thereof by at least one polymorphically-expressed cytochrome P450 isoform in the subject, as compared to the corresponding non-isotopically enriched compound.
72. The method as recited in claim 71, wherein the cytochrome P450 isoform is selected from the group consisting of CYP2C8, CYP2C9, CYP2C19, and CYP2D6.
73. The method as recited in claim 64, wherein said compound is characterized by decreased inhibition of at least one cytochrome P450 or monoamine oxidase isoform in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
74. The method as recited in claim 73, wherein said cytochrome P450 or monoamine oxidase isoform is selected from the group consisting of CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2G1, CYP2J2, CYP2R1, CYP2S1, CYP3A4, CYP3A5, CYP3A5P1, CYP3A5P2, CYP3A7, CYP4A11, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP4F11, CYP4F12, CYP4X1, CYP4Z1, CYP5A1, CYP7A1, CYP7B1, CYP8A1, CYP8B1, CYP11A1, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, CYP24, CYP26A1, CYP26B1, CYP27A1, CYP27B1, CYP39, CYP46, CYP51, MAOA, and MAOB.
75. The method as recited in claim 64, wherein the method affects the treatment of the disease while reducing or eliminating a deleterious change in a diagnostic hepatobiliary function endpoint, as compared to the corresponding non-isotopically enriched compound.
76. The method as recited in claim 75, wherein the diagnostic hepatobiliary function endpoint is selected from the group consisting of alanine aminotransferase (\u201cALT\u201d), serum glutamic-pyruvic transaminase (\u201cSGPT\u201d), aspartate aminotransferase (\u201cAST,\u201d \u201cSGOT\u201d), ALTAST ratios, serum aldolase, alkaline phosphatase (\u201cALP\u201d), ammonia levels, bilirubin, gamma-glutamyl transpeptidase (\u201cGGTP,\u201d \u201c\u03b3-GTP,\u201d \u201cGGT\u201d), leucine aminopeptidase (\u201cLAP\u201d), liver biopsy, liver ultrasonography, liver nuclear scan, 5\u2032-nucleotidase, and blood protein.
77. A method for the treatment, prevention, or amelioration of one or more symptoms of a NDMA receptor-mediated disorder in a subject, by administering a therapeutically effective amount of a compound as recited in claim 19.
78. The method as recited in claim 77, wherein the NDMA receptor-mediated disorder is selected from the group consisting of nociceptive pain, neuropathic pain, phantom limb pain, ischemic pain, stroke, sepsis, inflammation, opioid tolerance, Alzheimer’s disease, and burn.
79. The method as recited in claim 77, wherein the NMDA receptor-mediated disorder can be lessened, alleviated, or prevented by using as agent selected from the group consisting of an anesthetic, analgesic, entheogen, therapeutic cataleptic, and neuroprotectant.
80. The method as recited in claim 79, wherein the anesthetic promotes general anaesthesia.
81. The method as recited in claim 77, wherein the NMDA receptor-mediated disorder can be lessened, alleviated, or prevented by administering a NDMA receptor modulator.
82. The method as recited in claim 77, wherein said compound has at least one of the following properties:
a) decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b) increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c) decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d) increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e) an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
83. The method as recited in claim 77, wherein said compound has at least two of the following properties:
a) decreased inter-individual variation in plasma levels of said compound or a metabolite thereof as compared to the non-isotopically enriched compound;
b) increased average plasma levels of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
c) decreased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound;
d) increased average plasma levels of at least one metabolite of said compound per dosage unit thereof as compared to the non-isotopically enriched compound; and
e) an improved clinical effect during the treatment in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
84. The method as recited in claim 77, wherein the method affects a decreased metabolism of the compound per dosage unit thereof by at least one polymorphically-expressed cytochrome P450 isoform in the subject, as compared to the corresponding non-isotopically enriched compound.
85. The method as recited in claim 84, wherein the cytochrome P450 isoform is selected from the group consisting of CYP2C8, CYP2C9, CYP2C19, and CYP2D6.
86. The method as recited in claim 77, wherein said compound is characterized by decreased inhibition of at least one cytochrome P450 or monoamine oxidase isoform in said subject per dosage unit thereof as compared to the non-isotopically enriched compound.
87. The method as recited in claim 86, wherein said cytochrome P450 or monoamine oxidase isoform is selected from the group consisting of CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2A13, CYP2B6, CYP2C8, CYP2C9, CYP2C18, CYP2C19, CYP2D6, CYP2E1, CYP2G1, CYP2J2, CYP2R1, CYP2S1, CYP3A4, CYP3A5, CYP3A5P1, CYP3A5P2, CYP3A7, CYP4A11, CYP4B1, CYP4F2, CYP4F3, CYP4F8, CYP4F11, CYP4F12, CYP4X1, CYP4Z1, CYP5A1, CYP7A1, CYP7B1, CYP8A1, CYP8B1, CYP11A1, CYP11B1, CYP11B2, CYP17, CYP19, CYP21, CYP24, CYP26A1, CYP26B1, CYP27A1, CYP27B1, CYP39, CYP46, CYP51, MAOA, and MAOB.
88. The method as recited in claim 77, wherein the method affects the treatment of the disease while reducing or eliminating a deleterious change in a diagnostic hepatobiliary function endpoint, as compared to the corresponding non-isotopically enriched compound.
89. The method as recited in claim 88, wherein the diagnostic hepatobiliary function endpoint is selected from the group consisting of alanine aminotransferase (\u201cALT\u201d), serum glutamic-pyruvic transaminase (\u201cSGPT\u201d), aspartate aminotransferase (\u201cAST,\u201d \u201cSGOT\u201d), ALTAST ratios, serum aldolase, alkaline phosphatase (\u201cALP\u201d), ammonia levels, bilirubin, gamma-glutamyl transpeptidase (\u201cGGTP,\u201d \u201c\u03b3-GTP,\u201d \u201cGGT\u201d), leucine aminopeptidase (\u201cLAP\u201d), liver biopsy, liver ultrasonography, liver nuclear scan, 5\u2032-nucleotidase, and blood protein.