A double-blind study for the migraine prophylaxis by propranol and CH is reported. Before (Rao et al. 2000), but our study, we performed all prophylaxis to the last, but protective efficacy for the migraine uses CH only to refractory patients with frequent migraine. Therefore, it was shown to our study that CH was effective for the refractory patients with frequent migraine.
Involvement of the trigeminal-vascular system (Mathew 2001; Silberstein 2004) is generally considered the most likely cause of migraine. According to this theory, release of serotonin from platelets induces cerebral vasoconstriction and decreases cerebral blood flow, inducing aura, including scintillating scotomata. Subsequent serotonin depletion leads to cerebral vasodilatation and stimulation of the trigeminal nerve, which extends around vessels such as intracranial large vessels and the dura mater, inducing neurogenic inflammation and thus triggering migraine (Ollat 1992; Greek 2006; Hammon & Hoyer 2008). There are seven types of serotonin receptors. The serotonin 1 and 2 receptors are involved in cerebral vasoconstriction, and the serotonin 1 receptor exists predominantly in cerebral blood vessels. Furthermore, several subtypes of the serotonin 1 receptor have been identified, and among them, the serotonin 1B and 1D receptors are considered to be involved in cerebral vasoconstriction and in causing migraine (Ferrari et al. 2001; Wolff et al. 2003; Filip & Bader 2009). It has also been shown that binding of serotonin to the serotonin 1D receptor at trigeminal nerve terminals inhibits release of vasoactive peptides, including calcitonin gene-related peptides.
CH, which we used in this study, is generally used for migraine in pediatric patients, but not adult patients. In addition to its antihistaminic action, CH exerts antiserotonin and anticholinergic actions, and antagonizes histamine and serotonin receptors. It does not inhibit or chemically inactivate release of histamine and serotonin, but competitively and reversibly antagonizes histamine and serotonin at receptor sites. Therefore, we conclude that CH showed superior prophylactic efficacy to commonly used drugs in our patients owing to its inhibition of the release of vasoactive peptides, including calcitonin gene-related peptides, with simultaneous inhibition of both serotonin 1B and 1D receptors and prevention of neurogenic inflammation caused by stimulation of the trigeminal nerve in patients with refractory migraine (Villalon & Olsen 2009). Its greater efficacy in patients with allergic rhinitis and refractory migraine is considered to be attributable its antihistaminic action.
Based on the present results, we suggest that even adult patients who do not respond to multiple drugs currently used for migraine prophylaxis should be given preventive therapy with CH. However, since the antiserotonin action of CH is stronger than that of lysergic acid diethylamide (LSD), great care is needed to prevent the onset of visual hallucinations and confusion, especially at higher doses. Also, weight gain should be anticipated due to stimulation of the feeding center by the anticholinergic action of this drug. Long-term treatment with CH should be avoided.