Anti-migraine compounds fail to modulate the propagation of cortical spreading depression in the cat

Abstract

Leao's cortical spreading depression (SD) is often cited as the pathophysiological substrate for the neurological symptoms of migraine with aura. If this is the case it might be expected that drugs useful as anti-migraine agents, particularly those useful in prophylaxis, may alter or prevent SD. Indeep it has been suggested that the anti-migraine compound dihydroergotamine (DHE) blocks or reduces the speed of propagation of SD in the rabbit. In this study we attempted to further investigate the effects of DHE and other anti-migraine drugs on SD by measuring cortical blood flow with laser Doppler flowmetry (CBFLDF) and cortical single unit activity in the alpha-chloralose-anaesthetised cat. The following substances were tested: DHE, acetylsalicylic acid, lignocaine, metoprolol, clonazepam and valproate. The NMDA-receptor blocker MK-801 and halothane (1.5%) were used as reference substances that reliably block SD. The outcome measures were speed of propagation of the wave of SD across the cortex and the CBFLDF increase during the hyperaemic phase of SD. Data were taken from three control episodes (60 min apart) and after drug administration. The rate of propagation was significantly reduced from the first control period (3.0 +/- 0.3 mm/min) to the subsequent 2 control observations (2.3 +/- 0.1 mm/min) even without any drug treatment. Following the control observations the test drug was administered and a further SD elicited. This fourth SD was reliably blocked by MK-801 and halothane. None of the other test drugs inhibited SD, reduced the rate of propagation or changed the amplitude of the CBFLDF increase.(ABSTRACT TRUNCATED AT 250 WORDS)