Acta neurol. scandinav. 59, 154-155, 1979
SHORT COMMUNICATION
Department of Neurology, Odense University Holspital, Odense, Denmark
FPL 57787 and migraine prophylaxis A DOUBLE-BLIND CROSS-OVER STUDY
NILSKOCH-HENRIKSEN AND PERSEHESTED In a double-blind cross-over trial with placebo, FPL 57787, a chromone derivate, was tested on 15 patients as a prophylactic against migraine. There was found to’ be no, efiect. Key words: Allergy - cromone derivative bition - migraine prophylaxis
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mast cell de gra da tion inhi-
A chromoae derivate (6,7,8,9-tetrahydro-5-hydroxy-4-o~x~lO-pr~yl-4H-naphto(2,3-b) pyran-2-carboxylic acid) with the provisional name FPL 57787, possessing stabilizing propertes on the granula of mast cells, has been proposed as a prophylactic remedy against migraine. No studies have yet been reported concerning this effect. Recent studies indicate an antiallergic effect in peroral doses similar to that used in this trial (Augestein 1977). MATERIAL AND METHODS Fifteen outpatients with frequent attacks of migraine (according t o Ad Hoc Committee on Classification of Headache 1962), volunteered for this study. Patients with other disorders were not included; also patients with less than four attacks in a 6-week pretrial period, patients unable t o distinguish attacks of migraine from other sorts of headache, and patients who were unable t o complete diary cards properly, were all excluded. The patients received FPL 57787, 6 mg four times a day, and placebo in randomized sequence in two 6-week periods, separated by a 2-week “wash out” period. The patients recorded the number, duration, and severity of migraine attacks on diary cards, which were collected every 14 days together with blood and urine analysis. A nonparametric statistical test (Wilcoxon’s test for paired data) was used with a probability level of 0.05 being taken as significant. RESULTS N o difference was folund between the prophylactic effect against migraine of FPL 57781 and placebo according t o the number of migraine days, the severity or duration of attacks (P >> 0.1).
SIDE EFFECTS Three patients complained of mild and transcient gastrointestinal troubles. One patient complained of persistent dizziness. No abnoirmal laboratory data were fojund. 0001-6314/79/020154-02 $0.2.50/0 @ 1979 Munksgaard, Copenhagen
155 DISCUSSION Sicuteri (1963) showed discharge of granula of mast cells in biopsies from skin and scalp taken from the affected side under migraine attacks, indicating a link between migraine attack and release of mast cell compounds; also Thonnard-Neumann & Taylor (1968) showed an increased number of ear blood basophilic leucocytes taken from the affected side under migraine attacks. Providing the membrane stabilizing properties of FPL 57787 on mast cell granula, the lack of effect in this trial could be explained in two ways: 1) The dosage might be insufficient, or 2) degranulation of mast cells may be a feature secondary t o the migraine attack and not necessary for its development. REFERENCES Ad Hoc Committee on Classification of Headache (1962): Classification of headache. J. Am. Med. Assoc. 179, 9, 127. Augstein, J. et al. (1977): New orally effective chromone derivatives for the treatment of asthma. In: Agents and Actions, vol. 7/4, pp. 443-445. Birkhauser Verlag, Basel. Sicuteri,F. (1963): Mast cells and their active substances: Their role in the pathogenesis of migraine. Headache 3, 86-92. Thonnard-Neumann, E. & W. L. Taylolr (1968): The basophilic leucocyte and migraine. Headache 8, 98-107. Received October 26, accepted November 8, 1978
Nils Koch-Henriksen, M.D. Klovervaenget 22 B DK-5000 Odense C Denmark
SHORT COMMUNICATION
Department of Neurology, Odense University Holspital, Odense, Denmark
FPL 57787 and migraine prophylaxis A DOUBLE-BLIND CROSS-OVER STUDY
NILSKOCH-HENRIKSEN AND PERSEHESTED In a double-blind cross-over trial with placebo, FPL 57787, a chromone derivate, was tested on 15 patients as a prophylactic against migraine. There was found to’ be no, efiect. Key words: Allergy - cromone derivative bition - migraine prophylaxis
-
mast cell de gra da tion inhi-
A chromoae derivate (6,7,8,9-tetrahydro-5-hydroxy-4-o~x~lO-pr~yl-4H-naphto(2,3-b) pyran-2-carboxylic acid) with the provisional name FPL 57787, possessing stabilizing propertes on the granula of mast cells, has been proposed as a prophylactic remedy against migraine. No studies have yet been reported concerning this effect. Recent studies indicate an antiallergic effect in peroral doses similar to that used in this trial (Augestein 1977). MATERIAL AND METHODS Fifteen outpatients with frequent attacks of migraine (according t o Ad Hoc Committee on Classification of Headache 1962), volunteered for this study. Patients with other disorders were not included; also patients with less than four attacks in a 6-week pretrial period, patients unable t o distinguish attacks of migraine from other sorts of headache, and patients who were unable t o complete diary cards properly, were all excluded. The patients received FPL 57787, 6 mg four times a day, and placebo in randomized sequence in two 6-week periods, separated by a 2-week “wash out” period. The patients recorded the number, duration, and severity of migraine attacks on diary cards, which were collected every 14 days together with blood and urine analysis. A nonparametric statistical test (Wilcoxon’s test for paired data) was used with a probability level of 0.05 being taken as significant. RESULTS N o difference was folund between the prophylactic effect against migraine of FPL 57781 and placebo according t o the number of migraine days, the severity or duration of attacks (P >> 0.1).
SIDE EFFECTS Three patients complained of mild and transcient gastrointestinal troubles. One patient complained of persistent dizziness. No abnoirmal laboratory data were fojund. 0001-6314/79/020154-02 $0.2.50/0 @ 1979 Munksgaard, Copenhagen
155 DISCUSSION Sicuteri (1963) showed discharge of granula of mast cells in biopsies from skin and scalp taken from the affected side under migraine attacks, indicating a link between migraine attack and release of mast cell compounds; also Thonnard-Neumann & Taylor (1968) showed an increased number of ear blood basophilic leucocytes taken from the affected side under migraine attacks. Providing the membrane stabilizing properties of FPL 57787 on mast cell granula, the lack of effect in this trial could be explained in two ways: 1) The dosage might be insufficient, or 2) degranulation of mast cells may be a feature secondary t o the migraine attack and not necessary for its development. REFERENCES Ad Hoc Committee on Classification of Headache (1962): Classification of headache. J. Am. Med. Assoc. 179, 9, 127. Augstein, J. et al. (1977): New orally effective chromone derivatives for the treatment of asthma. In: Agents and Actions, vol. 7/4, pp. 443-445. Birkhauser Verlag, Basel. Sicuteri,F. (1963): Mast cells and their active substances: Their role in the pathogenesis of migraine. Headache 3, 86-92. Thonnard-Neumann, E. & W. L. Taylolr (1968): The basophilic leucocyte and migraine. Headache 8, 98-107. Received October 26, accepted November 8, 1978
Nils Koch-Henriksen, M.D. Klovervaenget 22 B DK-5000 Odense C Denmark
