Nomenclature for flunarizine,cinnarizine,and lomerizine

To the Editor,

Flunarizine, cinnarizine, and lomerizine have been used for the prophylactic treatment of migraine in certain countries and have been classified as calcium channel blockers (CCBs). These drugs, however, have other pharmacological characteristics in addition to those of CCBs. In addition to the T-type calcium channel blocking effect, flunarizine, cinnarizine, and lomerizine have antihistamine and anti-serotonin effects. Moreover, flunarizine and cinnarizine, but not lomerizine, have anti-dopaminergic effects (Table 1) (1). Other agents with antihistamine effects, such as cyproheptadine and pizotifen, are also effective in migraine prevention. In contrast, other T-type CCBs, including verapamil, diltiazem, and nimodipine, do not show a definitive migraine prevention effect. Similarly, L-type CCBs, including nimodipine, nifedipine, and nicardipine, do not demonstrate a migraine prevention effect.

Table 1.

Migraine prevention effect of medications with antihistamine, anti-dopamine, anti-serotonin or calcium channel blocking properties.

	Migraine prevention	Antihistamine	Anti-dopamine	Anti-serotonin	T-type CCB (low voltage)	L-type CCB (high voltage)
Flunarizine	+	+ (H1 receptor)	+ (D2 receptor)	+ (5-HT2 receptor)	+, by blocking VDCC	−
Cinnarizine	+	+ (H1 receptor)	+ (D1 and D2 receptor)	+ (5-HT2 receptor)	+, by blocking VDCC	−
Lomerizine	+	+ (H1 receptor)	− in vivo	+ (5-HT2 receptor)	+, by blocking VDCC	−
Cyproheptadine	+	+ (H1 receptor)	−	+ (5-HT2 receptor)	−	−
Pizotifen	+	+ (H1 receptor)	−	+ (5-HT1 and 5-HT2 receptor)	−	−
Methysergide	+	−	−	+ (5-HT2 receptor)	−	−
Verapamil	U	−	−	Weak serotonin inhibition	+, by blocking VDCC	−
Diltiazem	U	−	−	Weak serotonin inhibition	+, by blocking VDCC	−
Nimodipine	U	−	−	Weak serotonin inhibition	−	+
Nifedipine	NR	−	−	−	−	+
Nicardipine	NR	−	−	−	−	+
Domperidone	+	−	+(D2 and D3 receptor)	−	−	−
Quetiapine	+	+ (H1 receptor)	+(D1, D2, D3 and D4 receptor)	+ (5-HT2 receptor)	−	−
Metoclopramide	+	−	+ (D2 receptor)	+ (5-HT3 and5-HT4 receptor)	−	−

CCB: calcium channel blocker; NR: not reported; U: inadequate date or conflicting data; VDCC: voltage-dependent calcium channel; +: effect presence; −: no effect.

Appropriate nomenclature can lead to the enhanced understanding of a disease as well as the proper identification of drug mechanisms. Although the pharmacological characteristics of a drug may not explain the exact mechanisms of a particular drug function, the pharmacological characteristics of drugs with and without migraine prevention effects propose that the T-type or L-type calcium channel blocking alone cannot account for the prevention effects of migraine.

It remains unclear whether histamine receptor blocking has a definitive migraine prevention effect; however, many histamine H1 and H2 receptor blocking agents show a significant effect in migraine prevention (2). Flunarizine, cinnarizine, and lomerizine were given these International Nonproprietary Names (INN) based on their antihistamine effect (-izine) (3). Considering the pharmacological characteristics of flunarizine, cinnarizine, and lomerizine, and the pharmacological characteristics of other drugs showing migraine preventive effects, it would be more appropriate to classify flunarizine, cinnarizine, and lomerizine as antihistamines or assign them to another class name instead of CCBs.