Abstract It has been suggested that spreading depression may play a role in triggering classical migraine. In this study the retinal spreading depression was used as a pharmacological tool to test the neuronal effects of several common antimigraine drugs. As the chicken retina is void of any blood vessels the observed effects must be of pure neuronal origin. It is shown that propranolol, sumatriptan, methysergide, paracetamol and acetylsalicyclic acid decrease the propagation velocity of retinal spreading depression waves, accelerate the recovery of the optical and electrical signal and reduce the amplitude of the negative potential shift, concomitant with the spreading depression. Barbiturate increases the spreading velocity, and the amplitude of the potential shift. Ergotamine, clonidine, lisuride and iprazochrome have no significant influence on retinal spreading depression.