8'-hydroxy-dihydroergotamine compounds and compositions

Abstract

8′-Hydroxy-Dihydroergotamine (8′-OH DHE) medicinal compounds, compositions, and dosage forms containing such compositions are provided. Also provided herein are methods of treatment, prevention, or amelioration of migraine disorders using the compounds, compositions, dosage forms and administration techniques disclosed herein.

What is claimed is: 
     
         1 . A method of treating a migraine disease, condition or disorder, said method comprising administering a therapeutically effective amount of 8′-hydroxy-dihydroergotamine (8′-OH DHE) to a subject in need of such treatment, wherein the 8′-OH DHE has the following structure: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , wherein said treatment comprises a reduction in one or more migraine symptoms. 
     
     
         3 . The method of  claim 1 , wherein said treatment comprises partial relief from at least one migraine symptom. 
     
     
         4 . The method of  claim 3 , wherein said treatment further comprises sustained relief from the at least one migraine symptom. 
     
     
         5 . The method of  claim 2 , wherein said treatment is further characterized by not inducing one or more drug-induced side-effects. 
     
     
         6 . The method of  claim 5 , wherein said one or more drug-induced side-effect is selected from nausea, emesis, chest tightness and cardiovascular effects. 
     
     
         7 . The method of  claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C max ) of 8′-OH DHE that is less than 500 pg/mL. 
     
     
         8 . The method of  claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C max ) of 8′-OH DHE that is less than 2,500 pg/mL. 
     
     
         9 . The method of  claim 1 , wherein said 8′-OH DHE is administered at a rate sufficient to provide a maximum circulating plasma level (C max ) of 8′-OH DHE that is less than 5,000 pg/mL. 
     
     
         10 . The method of  claim 1 , wherein said 8′-OH DHE is administered in the form of a solution, suspension, tablet, dispersible tablet, pill, capsule, powder, sustained release composition, an elixir, a sterile solution or suspension suitable for parenteral administration, a topical dosage form, a transdermal dosage form, a nasal dosage form, or a pulmonary dosage form suitable for inhalation administration. 
     
     
         11 . The method of  claim 10 , wherein said 8′-OH DHE is administered in a pulmonary dosage form suitable for inhalation administration. 
     
     
         12 . The method of  claim 1 , wherein said 8′-OH DHE is administered using a nebulizer, a DPI device, a MDI device, or a pMDI device. 
     
     
         13 . The method of  claim 11 , wherein said 8′-OH DHE composition is administered using a pMDI device. 
     
     
         14 . The method of  claim 1  or  13 , wherein the subject is a human.