ABSTRACT
Non-pharmacological therapy of primary headache conditions including chronic daily headache (CDH) is not well-studied. Barton and Blanchard report on their experience with intensive self-regulatory treatment in a cohort of patients with CDH. This negative trial provides preliminary observations that need further investigations in controlled, adequately powered clinical study.
Subject(s)
Biofeedback, Psychology , Cognitive Behavioral Therapy , Headache Disorders/therapy , Muscle Relaxation , Self Care , Adult , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Research Design , Treatment FailureABSTRACT
The introduction of sumatriptan, a selective 5-HT(1B/1D) agonist, for the treatment of migraine sparked a new era of drug research in this field. Many novel targets have since been developed, and tested in the clinic. The promise of these approaches is to deliver an anti-migraine compound with the optimal efficacy and safety profile. In this chapter, blind alleys in anti-migraine development are discussed. The failing soldiers have included the NK-1 antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93, the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists (PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising targets failed to demonstrate clinical efficacy, while others were stopped for preclinical toxicity.
Subject(s)
Endothelin-1/antagonists & inhibitors , Migraine Disorders/drug therapy , Neurokinin-1 Receptor Antagonists , Serotonin Receptor Agonists/therapeutic use , Drug Evaluation, Preclinical , Humans , Serotonin Receptor Agonists/adverse effectsABSTRACT
The authors investigated early human focal ischemia with phosphorus-31 nuclear magnetic resonance spectroscopy at 1.89 T to characterize the temporal evolution and relationship of brain pH and phosphate energy metabolism. Data from 65 symptomatic patients were prospectively studied; none of the patients had had ischemic stroke in the internal carotid artery territory before. Twenty-eight neurologically normal individuals served as control subjects. Serial ischemic brain pH levels indicated a progression from early acidosis to subacute alkalosis. When acidosis was present there was a significant elevation in the relative signal intensity of inorganic phosphate (Pi) and significant reductions in signal intensities of alpha-adenosine triphosphate (ATP) and gamma-ATP compared with those of control subjects. Ischemic brain pH values directly correlated with the relative signal intensity of phosphocreatine (PCr) and the PCr index and inversely correlated with the signal intensity of Pi. There was a general lack of correlation between either ischemic brain pH or phosphate energy metabolism and the initial clinical stroke severity. The data suggest a link between high-energy phosphate metabolism and brain pH, especially during the period of ischemic brain acidosis, and the authors propose that effective acute stroke therapy should be instituted during this period.