Method of reducing neuronal cell death with haloalkylamines

Abstract

The present invention is directed to pharmaceutical compositions and methods of treating traumatic brain injury (TBI). The invention is also directed to pharmaceutical compositions and methods of treating a transient hypoxic and/or ischemic condition in the central nervous system. More specifically, the present invention is directed to pharmaceutical compositions and methods of reducing the occurrence of nerounal cell death in the central nervous system, such as, reducing the occurrence brain cell death in the hippocampus and/or the cortex.

1 . A method of treating a subject having a transient hypoxic and/or ischemic condition in the central nervous system or traumatic brain injury (TBI), the method comprising administering to the subject a therapeutically effective amount of a haloalkylamine. 
     
     
         2 . The method of  claim 1 , further comprising determining that the subject has had a transient hypoxic and/or ischemic condition and is at risk of neuronal cell death caused by the condition, wherein the condition is caused by low blood pressure, blood loss, a heart attack, a spinal cord injury (SCI), strangulation, surgery, a stroke, a spinal cord infarction, ischemic optic neuropathy, air-way blockage, or neonatal hypoxia or ischemia. 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , further comprising determining that the subject has had a TBI event and is at risk of neuronal cell death, wherein the TBI event is selected from the group consisting of whiplash, a blast wave impact, and blunt force trauma. 
     
     
         5 . The method of  claim 1 , wherein the haloalkylamine reduces the occurrence of neuronal cell death in the subject. 
     
     
         6 . The method of  claim 4 , wherein in haloalkylamine reduces the occurrence of neuronal brain cell death in the striatum, hippocampus, or the cortex of the subject. 
     
     
         7 . A method of reducing the occurrence of neuronal cell death in the central nervous system of a subject at risk thereof, the method comprising administering to the subject a haloalkylamine in an amount sufficient to reduce neuronal cell death in the central nervous system of the subject. 
     
     
         8 . The method of  claim 7  further comprising determining that the subject has had a transient hypoxic and/or ischemic condition and is at risk of neuronal cell death caused by the condition. 
     
     
         9 . The method of  claim 7  further comprising determining that the subject has had a traumatic brain injury (TBI) event before administration, wherein the haloalkylamine is administered with a pharmaceutically acceptable carrier. 
     
     
         10 . The method of  claim 1 , wherein the haloalkylamine is in unit dosage amounts of 0.5 mg/kg body weight to 20 mg/kg body weight. 
     
     
         11 . (canceled) 
     
     
         12 . The method of  claim 1 , wherein the haloalkylamine is in an extended release formulation. 
     
     
         13 . The method of  claim 1 , wherein the haloalkylamine is administered within 24 hours after onset of the transient hypoxic and/or ischemic condition. 
     
     
         14 . The method of  claim 1 , wherein the haloalkylamine is administered within 18 hours after onset of the transient hypoxic and/or ischemic condition. 
     
     
         15 . The method of  claim 1 , wherein the haloalkylamine is administered in a single dose within 16 hours after onset of low blood pressure, blood loss, a heart attack, a TBI event, a SCI event, strangulation, surgery, a stroke, a spinal cord infarction, ischemic optic neuropathy, air-way blockage, or neonatal hypoxia or ischemia. 
     
     
         16 . The method of  claim 1 , wherein the administering is via an intravenous injection. 
     
     
         17 . The method of  claim 1 , wherein the haloalkylamine is selected from the group consisting of phenoxybenzamine and dibenamine. 
     
     
         18 - 37 . (canceled) 
     
     
         38 . The method of  claim 7 , wherein the haloalkylamine is in unit dosage amounts of 0.5 mg/kg body weight to 20 mg/kg body weight. 
     
     
         39 . The method of  claim 7 , wherein the haloalkylamine is administered within 24 hours after onset of the transient hypoxic and/or ischemic condition. 
     
     
         40 . The method of  claim 7 , wherein the haloalkylamine is selected from the group consisting of: phenoxybenzamine and dibenamine.