METHODS OF TREATMENT USING AN AMPHETAMINE PRODRUG
Disclosed are methods of treatment of various conditions and disorders, and symptoms associated therewith, including, for example, fatigue and/or inattention associated with various conditions and disorders, using homoarginine-amphetamine prodrug and/or conjugate, or salts thereof.
1 . A method of treating fatigue in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
2 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with chronic fatigue syndrome.
3 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with myalgic encephalomyelitis.
4 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with fibromyalgia.
5 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with multiple sclerosis.
6 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with major depressive disorder.
7 . The method of claim 1 , wherein the fatigue is in a patient diagnosed with a metabolic disorder.
8 . The method of claim 7 , wherein the metabolic disorder is obesity, appetite related symptoms of the Prader Willi Syndrome, Type 1 diabetes mellitus, Type 2 diabetes mellitus, or a combination thereof.
9 . The method of claim 1 , wherein the fatigue is post-cancer therapy fatigue caused by cancer therapy, wherein the cancer therapy is chemotherapy, radiation therapy, surgery, or combinations thereof.
10 . The method of claim 9 , wherein the chemotherapy is selected from the group consisting of methotrexate, cytarabine, vincristine, dexamethasone, hydrocortisone, and prednisone.
11 . The method of claim 9 , wherein the chemotherapy is for acute lymphoblastic leukemia, breast cancer, or a malignant brain cancer.
12 . The method of claim 11 , wherein the malignant brain cancer is a glioma, astrocytoma, medulloblastoma, ependymoma, or brain stem glioma.
13 . A method of treating fatigue in a patient diagnosed with chronic fatigue syndrome, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
14 . A method of treating fatigue in a patient diagnosed with myalgic encephalomyelitis, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
15 . A method of treating fatigue in a patient suffering from fibromyalgia, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
16 . A method of treating fatigue in a patient suffering from multiple sclerosis which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
17 . A method of treating fatigue in a patient suffering from major depressive disorder which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
18 . The method of claim 17 , wherein the patient is receiving concurrent treatment with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
19 . The method of claim 17 or 18 , wherein the patient's fatigue was inadequately treated with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
20 . A method of treating fatigue in a cancer patient caused by chemotherapy, radiation therapy, surgery, or a combination thereof, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
21 . The method of any of claims 1 - 20 , further comprising treating cognitive dysfunction.
22 . The method of any of claims 1 - 21 , further comprising treating inattention.
23 . A method of treating cognitive dysfunction which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
24 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with chronic fatigue syndrome.
25 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with myalgic encephalomyelitis.
26 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with fibromyalgia.
27 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with multiple sclerosis.
28 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with major depressive disorder.
29 . The method of claim 23 , wherein the cognitive dysfunction is in a patient diagnosed with a metabolic disorder.
30 . The method of claim 29 , wherein the metabolic disorder is obesity, appetite related symptoms of the Prader Willi Syndrome, Type 1 diabetes mellitus, Type 2 diabetes mellitus, or a combination thereof.
31 . The method of claim 23 , wherein the cognitive dysfunction is post-cancer therapy cognitive dysfunction caused by cancer therapy, wherein the cancer therapy is chemotherapy, radiation therapy, surgery, or combinations thereof.
32 . The method of claim 31 , wherein the chemotherapy is selected from the group consisting of methotrexate, cytarabine, vincristine, dexamethasone, hydrocortisone, and prednisone.
33 . The method of claim 31 , wherein the chemotherapy is for acute lymphoblastic leukemia, breast cancer, or a malignant brain cancer.
34 . The method of claim 33 , wherein the malignant brain cancer is a glioma, astrocytoma, medulloblastoma, ependymoma, or brain stem glioma.
35 . A method of treating cognitive dysfunction in a patient diagnosed with chronic fatigue syndrome, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
36 . A method of treating cognitive dysfunction in a patient diagnosed with myalgic encephalomyelitis, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
37 . A method of treating cognitive dysfunction in a patient suffering from fibromyalgia, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
38 . A method of treating cognitive dysfunction in a patient suffering from multiple sclerosis which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
39 . A method of treating cognitive dysfunction in a patient suffering from major depressive disorder which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
40 . The method of claim 39 , wherein the patient is receiving concurrent treatment with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
41 . The method of claim 39 or 40 , wherein the patient's cognitive dysfunction was inadequately treated with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
42 . A method of treating cognitive dysfunction in a cancer patient caused by chemotherapy, radiation therapy, surgery, or a combination thereof, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
43 . The method of any of claims 23 - 42 , further comprising treating fatigue.
44 . The method of any of claims 23 - 43 , further comprising treating inattention.
45 . The method of any of claims 23 - 44 , wherein the cognitive dysfunction is a short-term memory problem, an attention problem, a concentration problem, a planning problem, or a combination thereof.
46 . A method of treating inattention which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
47 . The method of claim 46 , wherein the inattention is in a patient diagnosed with chronic fatigue syndrome.
48 . The method of claim 46 , wherein the inattention is in a patient diagnosed with myalgic encephalomyelitis.
49 . The method of claim 46 , wherein the inattention is in a patient diagnosed with fibromyalgia.
50 . The method of claim 46 , wherein the inattention is in a patient diagnosed with multiple sclerosis.
51 . The method of claim 46 , wherein the inattention is in a patient diagnosed with major depressive disorder.
52 . The method of claim 46 , wherein the inattention is in a patient diagnosed with a metabolic disorder.
53 . The method of claim 52 , wherein the metabolic disorder is obesity, appetite related symptoms of the Prader Willi Syndrome, Type 1 diabetes mellitus, Type 2 diabetes mellitus, or a combination thereof.
54 . The method of claim 46 , wherein the inattention is post-cancer therapy inattention caused by cancer therapy, wherein the cancer therapy is chemotherapy, radiation therapy, surgery, or combinations thereof.
55 . The method of claim 54 , wherein the chemotherapy is selected from the group consisting of methotrexate, cytarabine, vincristine, dexamethasone, hydrocortisone, and prednisone.
56 . The method of claim 45 , wherein the chemotherapy is for acute lymphoblastic leukemia, breast cancer, or a malignant brain cancer.
57 . The method of claim 56 , wherein the malignant brain cancer is a glioma, astrocytoma, medulloblastoma, ependymoma, or brain stem glioma.
58 . A method of treating inattention in a patient diagnosed with chronic fatigue syndrome, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
59 . A method of treating inattention in a patient diagnosed with myalgic encephalomyelitis, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
60 . A method of treating inattention in a patient suffering from fibromyalgia, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
61 . A method of treating inattention in a patient suffering from multiple sclerosis which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
62 . A method of treating inattention in a patient suffering from major depressive disorder which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
63 . The method of claim 62 , wherein the patient is receiving concurrent treatment with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
64 . The method of claim 62 or 63 , wherein the patient's inattention was inadequately treated with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
65 . A method of treating inattention in a cancer patient caused by chemotherapy, radiation therapy, surgery, or a combination thereof, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
66 . The method of any of claims 46 - 65 , further comprising treating cognitive dysfunction.
67 . The method of any of claims 46 - 66 , further comprising treating fatigue.
68 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 wherein the amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate is initially administered prior to the cancer therapy.
69 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate is initially administered after cancer therapy and before the patient is diagnosed with fatigue caused by chemotherapy or radiation therapy.
70 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate is initially administered after cancer therapy and after the patient is diagnosed with fatigue caused by chemotherapy or radiation therapy.
71 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the patient received chemotherapy that was delivered directly to the central nervous system.
72 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the patient received systemic chemotherapy.
73 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the cancer therapy is radiation therapy.
74 . The method of claim 73 , wherein the radiation therapy is cranial radiation therapy.
75 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the cancer therapy is surgery.
76 . The method of claim 75 , wherein the surgery is cranial surgery.
77 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the cancer therapy is a combination of chemotherapy and radiation therapy.
78 . The method of any of claim 9 - 12 , 20 - 22 , 31 - 34 , 42 - 45 , 54 - 57 , or 65 - 67 , wherein the cancer therapy is a combination of at least two of the following: chemotherapy, radiation therapy, or surgery.
79 . The method of any of claim 6 , 17 - 19 , 21 , 22 , 28 , 39 - 41 , 43 - 45 , 51 , 62 - 64 , 66 or 67 , wherein the patient is elderly.
80 . The method of any of claim 6 , 17 - 19 , 21 , 22 , 28 , 39 - 41 , 43 - 45 , 51 , 62 - 64 , 66 , 67 , or 79 wherein the patient is receiving concurrent treatment with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
81 . The method of any of claim 6 , 17 - 19 , 21 , 22 , 28 , 39 - 41 , 43 - 45 , 51 , 62 - 64 , 66 , 67 , 79 , or 80 wherein the patient's inattention was inadequately treated with a selective serotonin reuptake inhibitor, a serotonin norepinephrine reuptake inhibitor, a norepinephrine dopamine reuptake inhibitor, an atypical antidepressant, a tricyclic antidepressant, and/or a monoamine oxidase inhibitor.
82 . A method of treating fatigue, cognitive dysfunction, and/or inattention in a patient suffering from traumatic brain injury which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
83 . A method of treating fatigue, cognitive dysfunction, and/or inattention in a menopausal patient, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
84 . A method of treating fatigue, cognitive dysfunction, and/or inattention in a patient suffering from the negative symptoms of schizophrenia, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
85 . A method of treating fatigue, cognitive dysfunction, and/or inattention in a patient suffering from diabetes mellitus type I or type II, which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
86 . A method of treating cognitive dysfunction in a patient suffering from a cancer comprising administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof,
wherein the cognitive dysfunction is selected from the group consisting of: a short-term memory problem, an attention problem, a concentration problem, a planning problem, and a combination thereof; and
wherein the cognitive dysfunction appears before the patient receives chemotherapy.
87 . A method of treating a cognitive dysfunction in a patient suffering from a cancer comprising administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof,
wherein the cognitive dysfunction is selected from the group consisting of: a short-term memory problem, an attention problem, a concentration problem, a planning problem, and a combination thereof; and
wherein the cognitive dysfunction arises during chemotherapy or after the patient receives chemotherapy.
88 . A method of treating a wakefulness disorder which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
89 . A method of treating narcolepsy in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
90 . The method of claim 89 , wherein the patient is a child patient or an adult patient.
91 . A method of treating a wakefulness disorder caused by chemotherapy or radiation therapy which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
92 . A method of treating a behavior caused by hyperactivity and impulsivity in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
93 . A method of treating alcohol addiction in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
94 . A method of treating smoking addiction in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
95 . A method of treating symptoms of Fragile X syndrome in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
96 . A method of treating a metabolic disorder in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
97 . A method of treating obesity in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
98 . A method of treating an appetite related symptom of the Prader Willi Syndrome in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
99 . A method of treating Type 1 diabetes mellitus in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
100 . A method of treating Type 2 diabetes mellitus in a patient which comprises administering a therapeutically effective amount of an amphetamine-homoarginine conjugate or a salt of the amphetamine-homoarginine conjugate to a patient in need thereof.
101 . The method according to any one of claims 1 - 100 wherein the salt of the conjugate is mesylate, a hydrochloride, sulfate, oxalate, triflate, citrate, malate, tartrate, phosphate, nitrate, benzoate, or a mixture thereof.
102 . The method according to any one of claims 1 - 101 , wherein the amphetamine-homoarginine conjugate is 1-homoarginine-d-amphetamine dihydrochloride.
103 . The method according to any one of claims 1 - 102 , wherein the conjugate or the salt of the conjugate is in an amount of from about 1 mg to about 500 mg.
104 . The method according to any one of claims 1 - 103 , wherein the conjugate or the salt of the conjugate is in an amount of from about 5 mg to about 250 mg.
105 . The method according to any one of claims 1 - 104 , wherein the conjugate or the salt of the conjugate is in an amount of from about 10 mg to about 100 mg.