enalapril and Migraine-Disorders

1. Converting enzyme and neutral endopeptidase activities were both measured every 3 h by a fluorimetric method in plasma and cerebrospinal fluid of patients diagnosed as migraineurs with aura after lumbar puncture, which was performed 9 h after an acute oral dose of enalapril or placebo. 2. A reduced converting enzyme activity, as compared with placebo, was observed in patients who were given enalapril. On the other hand, neutral endopeptidase activity detected after enalapril did not differ from that measured after placebo. 3. The results seem to indicate that enalapril penetrates the blood-brain barrier in sufficient amounts to reduce converting enzyme activity. Moreover, neutral endopeptidase was not affected by enalapril. Therefore, those clinical effects of the drug which have been attributed to the involvement of central opioid mechanisms may depend on the inhibition of brain converting enzyme but not the inhibition of brain neutral endopeptidase.

Topics: Adult; Blood Pressure; Depression, Chemical; Enalapril; Endopeptidases; Female; Humans; Male; Migraine Disorders; Peptidyl-Dipeptidase A; Single-Blind Method

Seventeen patients with migraine headaches, occurring at least twice a month, were successfully treated with an ACE inhibitor for prophylaxis. Most were given enalapril, some used lisinopril. Duration of treatment ranged from 3 months to 3 years. Side effects were generally not noted. Cough occurred in four patients. The mechanism of action is unknown. The lack of side effects and the presence of clearly sustained benefit in this small group of migraineurs should prompt further study and use of this class of drugs for prophylaxis.

Topics: Adolescent; Adult; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Female; Humans; Lisinopril; Middle Aged; Migraine Disorders

The captopril-inhibited enzyme which forms [Met5]-enkephalin from [Met5]-enkephalin-Arg6,Phe7 in isolated rabbit ear artery was characterized further by using various natural substrate candidates/analogues ([Met5]-enkephalin-Arg6,Phe7 and its amide, [Met5]-enkephalin, angiotensin I and bradykinin), peptidase inhibitors such as captopril, enalaprilate and thiorphan and by endothelial removal. 10(-5) and 10(-4) M but not 10(-6) M captopril reduced the effectiveness of [Met5]-enkephalin-Arg6,Phe7 and potentiated the effect of bradykinin but did not affect markedly the action of the other peptides. Of the inhibitors, enalaprilate was less effective than captopril, and thiorphan had no effect. The [Met5]-enkephalin-Arg6,Phe7-->[Met5]-enkephalin conversion was not affected by endothelial removal. The substrate and inhibitor spectrum of this non-endothelial enzyme activity bears no relationship in other, hitherto characterized dipeptidylcarboxypeptidases/endopeptidases known to be involved in the metabolism of the tested peptides.

Topics: Amino Acid Sequence; Angiotensin I; Animals; Arteries; Bradykinin; Captopril; Disease Models, Animal; Ear, External; Enalapril; Endopeptidases; Endothelium, Vascular; Enkephalin, Methionine; Male; Migraine Disorders; Molecular Sequence Data; Rabbits; Substrate Specificity; Thiorphan