| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | February 22, 2000 |
| PATENT TITLE |
Treatment of oppositional defiant disorder |
| PATENT ABSTRACT | Norepinephrine reuptake inhibitors are used to treat oppositional defiant disorder |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | September 17, 1998 |
| PATENT REFERENCES CITED |
Chemical Abstract 89:157222, "Comparison of Inhibition of Monoamine Uptake by Cocaine, Methylphenidate, and Amphetamine", 1978. Journal of Abnormal Child Psychology. Barkley, R.A. et al., Adolescents with attention deficit hyperactivity disorder: mother-adolescent interactions, family beliefs and conflicts, and maternal psychopathology Abstract, Jun. 1992, vol. 20, No. 3, pp. 263-288. Diagnostic and Statistical Manual of Developmental Disorders, Fourth Edition (DSM-IV)pp. 78-94. POPPER, C.W.: "Antidepressants in the treatment of attention-deficit/hyperactivity disorder" The Journal of Clinical Psychiatry, vol. 58, no. suppl. 13, 1997, pp. 14-29. Greydanus, D. E. et al.: "The rebellious adolescent: Evaluation and management of oppositional and conduct disorders" Pediatric Clinics of North America, vol. 44, no. 6, pp. 1457-1485 |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
-------------------------------------------------------------------------------- We claim: 1. A method of treating oppositional defiant disorder comprising administration to a patient in need of such treatment an effective amount of a norepinephrine reuptake inhibitor selective for norepinephrine over other neurotransmitters. 2. A method of claim 1 wherein the norepinephrine reuptake inhibitor is selected from the group consisting of tomoxetine, reboxetine and a compound of formula I: ##STR2## wherein X is C.sub.1 -C.sub.4 alkylthio, and Y is C.sub.1 -C.sub.2 alkyl or a pharmaceutically acceptable salt thereof. 3. A method of claim 2 wherein the norepinephrine reuptake inhibitor is tomoxetine. 4. A method of claim 2 wherein the norepinephrine reuptake inhibitor is tomoxetine hydrochloride. 5. A method of claim 2 wherein the norepinephrine reuptake inhibitor is reboxetine. 6. A method of claim 2 wherein the norepinephrine reuptake inhibitor is (R)-N-methyl-3-(2-methylthiophenoxy)-3-phenylpropylamine. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
-------------------------------------------------------------------------------- FIELD OF THE INVENTION The invention belongs to the fields of pharmaceutical chemistry and psychiatric medicine, and provides a method of treatment of the psychiatric disorder known as oppositional defiant disorder. BACKGROUND OF THE INVENTION Children and adolescents suffering from oppositional defiant disorder exhibit a pattern of hostile, defiant, and negative behavior more often than is commonly observed in other individuals of the same mental age. They are argumentative with adults, are often angry and resentful, frequently lose their temper, swear, defy rules and requests from adults, and deliberately engage in annoying behavior. They also tend to not see themselves as a problem, but rather justify their behavior as a response to unreasonable circumstances. Oppositional defiant disorder (ODD) is many times treated with the same therapies employed for the treatment of Attention-deficit Hyperactivity Disorder (ADHD), e.g., methylphenidate (Ritalin.TM.), which exhibits noradrenergic and dopaminergic effects. Gross has demonstrated that certain ODD symptoms may be ameliorated by augmentation of standard ADHD therapies with buspirone in certain patients (Gross, J. Am. Acad. Child Adolesc. Psychiatry, 34(10), 1260 (1995)). Many patients are refractory to these treatments, or discontinue treatment due to intolerable side effects. Furthermore, due to the high potential for substance abuse in oppositional defiant disorder patients, the use of stimulants such as methylphenidate is problematic. The need for a safe and effective treatment for oppositional defiant disorder, without the disadvantages of current therapies, continues to be a concern of the psychiatric community. SUMMARY OF THE INVENTION The present invention provides a method of treating oppositional defiant disorder comprising the administration to a patient in need of such treatment of an effective amount of a norepinephrine reuptake inhibitor. DETAILED DESCRIPTION Many compounds, including those discussed at length below, are norepinephrine reuptake inhibitors, and no doubt many more will be identified in the future. In the practice of the present invention, it is intended to include reuptake inhibitors which show 50% effective concentrations of about 1000 nM or less, in the protocol described by Wong et al., Drug Development Research, 6, 397 (1985). The norepinephrine reuptake inhibitors useful for the method of the present invention are characterized in being selective for the inhibition of neurotransmitter reuptake relative to their ability to act as direct agonists or antagonists at other receptors. Norepinephrine reuptake inhibitors useful for the method of the present invention include, but are not limited to: Tomoxetine, (R)-(-)-N-methyl-3-(2-methylphenoxy)-3-phenylpropylamine, is usually administered as the hydrochloride salt. Tomoxetine was first disclosed in U.S. Pat. No. 4,314,081. The word "tomoxetine" will be used here to refer to any acid addition salt or the free base of the molecule. See, for example, Gehlert, et al., Neuroscience Letters, 157, 203-206 (1993), for a discussion of tomoxetine's activity as a norepinephrine reuptake inhibitor; The compounds of formula I: ##STR1## wherein X is C.sub.1 -C.sub.4 alkylthio, and Y is C.sub.1 -C.sub.2 alkyl or a pharmaceutically acceptable salt thereof. The compounds of formula I were described in U.S. Pat. No. 5,281,624, of Gehlert, Robertson, and Wong, and in Gehlert, et al., Life Sciences, 55(22), 1915-1920, (1995). The compounds are there taught to be inhibitors of norepinephrine reuptake in the brain. It is also explained that the compounds exist as stereoisomers, and that they accordingly include not only the racemates, but also the isolated individual isomers as well as mixtures of the individual isomers. For example, the compounds of formula I include the following exemplary species: N-ethyl-3-phenyl-3-(2-methylthiophenoxy)propylamine benzoate; (R)-N-methyl-3-phenyl-3-(2-propylthiophenoxy)propylamine hydrochloride; (S)-N-ethyl-3-phenyl-3-(2-butylthiophenoxy)propylamine; N-methyl-3-phenyl-3-(2-ethylthiophenoxy)propylamine malonate; (S)-N-methyl-3-phenyl-3-(2-tert-butylthiophenoxy)propylamine naphthalene-2-sulfonate; (R)-N-methyl-3-(2-methylthiophenoxy)-3-phenylpropylamine; Reboxetine (Edronax.TM.), 2-[.alpha.-(2-ethoxy)phenoxybenzyl]morpholine, is usually administered as the racemate. It was first taught by U.S. Pat. No. 4,229,449, which describes its utility for the treatment of depression. Reboxetine is a selective norepinephrine reuptake inhibitor. The term "reboxetine" will be used here to refer to any acid addition salt or the free base of the molecule existing as the racemate or either enantiomer; Duloxetine, N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine, is usually administered as the hydrochloride salt and as the (+) enantiomer. It was first taught by U.S. Pat. No. 4,956,388, which shows its high potency. The word "duloxetine" will be used here to refer to any acid addition salt or the free base of the molecule; Venlafaxine is known in the literature, and its method of synthesis and its activity as an inhibitor of serotonin and norepinephrine uptake are taught by U.S. Pat. No. 4,761,501. Venlafaxine is identified as compound A in that patent; and Milnacipran (N,N-diethyl-2-aminomethyl-1-phenylcyclopropanecarboxamide) is taught by U.S. Pat. No. 4,478,836, which prepared milnacipran as its Example 4. The patent describes its compounds as antidepressants. Moret et al., Neuropharmacology 24, 1211-19 (1985), describe its pharmacological activities as an inhibitor of serotonin and norepinephrine reuptake. All of the U.S. patents which have been mentioned above in connection with compounds used in the present invention are incorporated herein by reference. A preferred duloxetine enteric formulation is a pellet formulation comprising a) a core consisting of duloxetine and a pharmaceutically acceptable excipient; b) an optional separating layer; c) an enteric layer comprising hydroxypropylmethylcellulose acetate succinate (HPMCAS) and a pharmaceutically acceptable excipient; d) an optional finishing layer. The following example demonstrates the preparation of a preferred such formulation. |
| PATENT EXAMPLES | Available on request |
| PATENT PHOTOCOPY | Available on request |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |