Compositions, Devices, and Methods for Treating or Preventing Headaches

A method for treating or preventing a headache, comprising administering to a human subject a powdery pharmaceutical composition that comprises an active agent selected from the group consisting of a compound having a formula of:

• a pharmaceutically acceptable salt thereof, a complex thereof, a chelate thereof, a hydrate thereof, a polymorph thereof, and an ion pair thereof,
• wherein when applied to a human clinical study, said method produces a mean Visual Analog Scale score for measuring a nasal symptom less than about 20 if measured within 24 hours following said administration, wherein said Visual Analog Scale score is measured in a scale of 0 (none) to 100 (worst imaginable) based on each of the following nasal symptoms:
• nasal discomfort, nasal burning, nasal itching, nasal pain, nasal blockage or obstruction, abnormal taste, runny nose, and sneezing, and
• wherein:
• R1 is hydrogen, (C1-C4) alkyl, or (C1-C4) perfluoroalkyl;
• each R2 is independently hydrogen, halogen, alkyl, acyl, heteroalkyl, —NO2, —N3, —OH, —OR101, —NR102R103, —CONR104R105, or —CO2R106;
• R3 and R4 are independently hydrogen, deuterium, halogen, hydroxy, or methoxy;
• R5, R6, and R7 are independently hydrogen, (C1-C3) alkyl, or (C1-C3) perfluoroalkyl;
• R8 and R9 are independently hydrogen, (C1-C4) alkyl, or benzyl;
• R10, R11, R12, and R14 are independently hydrogen, halogen, —OH, (C1-C4) alkyl, —CO2R108, or —CONR109R110;
• R13 is hydrogen or halogen;
• R101, R102, R103, R104, R105, R106, R108, R109, and R110 are independently hydrogen, halogen, alkyl, acyl, aryl, arylalkyl, heteroalkyl, heteroaryl, or heteroarylalkyl;
• and
• n is 0, 1, 2, or 3.

A method for treating or preventing a headache, comprising administering to a human subject two or more unit doses of a pharmaceutical composition successively, or sequentially by about 1 or about 2 hours apart, in two or more devices, wherein said pharmaceutical composition comprises an active agent selected from the group consisting of a compound having a formula of:

• a pharmaceutically acceptable salt thereof, a complex thereof, a chelate thereof, a hydrate thereof, a polymorph thereof, and an ion pair thereof,
• wherein:
• R1 is hydrogen, (C1-C4) alkyl, or (C1-C4) perfluoroalkyl;
• each R2 is independently hydrogen, halogen, alkyl, acyl, heteroalkyl, —NO2, —N3, —OH, —OR101, —NR102R103, —CONR104R105, or —CO2R106;
• R3 and R4 are independently hydrogen, deuterium, halogen, hydroxy, or methoxy;
• R5, R6, and R7 are independently hydrogen, (C1-C3) alkyl, or (C1-C3) perfluoroalkyl;
• R8 and R9 are independently hydrogen, (C1-C4) alkyl, or benzyl;
• R10, R11, R12, and R14 are independently hydrogen, halogen, —OH, (C1-C4) alkyl, —CO2R108, or —CONR109R110;
• R13 is hydrogen or halogen;
• R101, R102, R103, R104, R105, R106, R108, R109, and R110 are independently hydrogen, halogen, alkyl, acyl, aryl, arylalkyl, heteroalkyl, heteroaryl, or heteroarylalkyl;
• and
• n is 0, 1, 2, or 3.