Prevalence of menstrually related migraine and nonmigraine primary headache in female students of Belgrade University.

OBJECTIVES: To determine prevalence and characteristics of menstrually related migraine and nonmigraine headache in female students of Belgrade University. METHODS: A questionnaire was administered to female students during randomly selected classes of the Schools of Medicine and Pharmacy. Diagnoses were assigned according to the criteria of the International Headache Society and MacGregor's stricter definition of "menstrual" migraine. RESULTS: Of 1943 female students (18 to 28 years old), 1298 (66.8%) had primary headaches. Among 1298 students with headache, 245 (12.6%) had migraine and 1053 (54.2%) had nonmigraine headache. The prevalence rates of migraine versus nonmigraine headache in relation to the menstrual cycle were: premenstrual, 0.9% versus 4.4%; menstrual, 1.5% versus 1.5%; menstrually associated, 6.1% versus 10.1%; menstrually unchanged, 2.7% versus 19.2%; and menstrually unrelated, 1.4% versus 18.9%. Female students with migraine had menstrually related attacks more frequently than students with nonmigraine headache (67.7% versus 29.5%). This difference was most prominent among students with menstrual migraine compared with students with menstrual nonmigraine headache (12.2% versus 2.7%). Exacerbation of migraine during menstruation was slightly more severe and more complex than exacerbation of nonmigraine headache. Female students with migraine versus nonmigraine headache did not differ significantly in age, age at onset of menarche, or age at onset of headache. Female students with migraine were significantly more likely to report a positive family history for migraine and menstrual migraine, severe attacks, reduced work activity, and aura. CONCLUSION: The results obtained are in accord with the prevailing opinion that there is a relationship between migraine and female sex hormones, and suggest that women with nonmigraine headache are also susceptible to hormonal fluctuations.

Urinary excretion of phenobarbital and its metabolite p-hydroxyphenobarbital in convulsing and non-convulsing patients.

As part of an investigation of phenobarbital (PB) pharmacokinetics in patients with status epilepticus (SE), urinary excretion of PB and its main metabolite, hydroxyphenobarbital (HPB), was studied in patients who had an episode of SE, as well as in non-convulsing ones. Eleven in-patients were studied:(group 1) five patients (4 M + 1 F; 48 +/- 28 years old; 64 +/- 6 kg body weight; mean +/- SD) with convulsive status epilepticus, and (group 2) six patients (5 M + 1 F; 37 +/- 13 years old; 71 +/- 15 kg body weight) with epilepsy, seizure-free at the moment of PB administration and without established anti-epileptic therapy. All subjects received a single intravenous dose of PB (15 mg/kg) at a rate of 100 mg/min. PB and HPB concentrations were measured by high performance liquid chromatography with UV detection at 220 nm in urine samples collected throughout 24 h. The comparison of pharmacokinetic parameters of urinary excretion of PB and HPB showed a statistically significant difference in the values of recovery of HPB and total barbiturate (higher values in the patients with SE) in 24 h urine. Differences in the excretion of PB between the two groups of patients--higher values in the patients who had had an episode of SE, and in urine flow--slightly elevated volumes in the same group, failed to reach statistical significance, probably due to the small number of participants in the study.

New and potent inhibitors of nitric oxide synthase reduce motor activity in mice.

Potent inhibitors of nitric oxide synthase (NOS), 3-bromo-7-nitro indazole, 1-(2-trifluoromethylphenyl)imidazole, S-methyl-L-thiocitrulline and 7-nitro indazole, reduced locomotion in mice. These results suggest that activity of NOS and corresponding NO release are of importance for normal locomotion.

Vigilance and EEG power in rats: effects of potent inhibitors of the neuronal nitric oxide synthase.

We examined the effects of potent neuronal nitric oxide synthase inhibitors, 3-bromo-7-nitro indazole (3-Br-7-NI) and S-methyl-L-thiocitrulline (S-Me-TC) on general behaviour, vigilance stages and electroencephalographic (EEG) power spectra in rats. In addition, we studied the effect of 7-nitro indazole (7-NI) on EEG power spectra in rats during dark and light periods. 3-Br-7-NI induced ptosis and decrease of slow wave sleep and rapid eye movement sleep in the rat. 7-NI and 3-Br-7-NI reduced the EEG power density in all frequency bands in the rat, suggesting a depression of central neuronal activity. This effect of 7-NI was more prominent during the day than during the night, indicating a circadian variation in the nitric oxide synthase (NOS) response to NOS inhibitor. EEG power was the most reduced in the 7-9 Hz range of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotion observed following administration of NOS inhibitors. Although S-Me-TC is the most potent NOS inhibitor in vitro experiments, it had less effect on vigilance and EEG power in the rat than other NOS inhibitors used in this study, probably due to its short lasting and blood pressure raising effect. The present results indicate that nitric oxide exerts an excitatory and circadian dependent effect in the central neuronal structures involved in the regulation of vigilance.

Anticonvulsant activity of new and potent inhibitors of nitric oxide synthase.

The effects of new and potent NOS inhibitors, S-methyl-L-thiocitrulline (S-Me-TC), 3-bromo 7-nitro indazole (3-Br-7-NI), and 1-(2-trifluoromethylphenyl) imidazole (TRIM), were examined on the pilocarpine-induced seizures in mice. 3-Br-7-NI and TRIM decreased the frequency of status epilepticus and mortality, while TRIM. In addition, significantly reduced the incidence of seizures. The latencies to onsets of seizures, status epilepticus, and mortality were significantly prolonged by all three NOS inhibitors, while duration of seizures was reduced by 3-Br-7-NI and TRIM. These data suggest an excitatory effect of NO in the neuronal structure involved in the pilocarpine-induced seizures.

Effect of ibogaine on naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats.

Ibogaine, an indole alkaloid, administered intracerebroventricularly 4-16 micrograms, attenuated a naloxone-precipitated withdrawal syndrome in chronic morphine-dependent rats. It appears that ibogaine has a more consistent effect on certain selective withdrawal signs related to the locomotion. This might explain an attenuating effect of ibogaine on some withdrawal signs. However, due to complex interaction of ibogaine with serotonin and other neurotransmitter systems, the mechanism of ibogaine antiwithdrawal effect remains unknown and requires further elucidation.

Effects of bestatin and phosphoramidon on the hypertensive response to physostigmine in the rat.

Intracarotid (IC) injection of bestatin produced a dose-dependent biphasic change in blood pressure (BP) of the rat, consisting of an initial short-lasting fall followed by a long-lasting increase. This effect was regularly depressed or abolished by IV injection of naloxone. IC injection of Leu-enkephalin also produced a biphasic BP response, with the same characteristics as that produced by IC injection of bestatin. This effect was also easily blocked by IV injection of naloxone. IC injection of bestatin significantly potentiated the BP response to IC injection of Leu-enkephalin. This potentiated response was blocked by naloxone. IC injection of both bestatin and phosphoramidon, whether separately or in combination, significantly depressed the hypertensive response to physostigmine. This depressive action of bestatin and phosphoramidon on physostigmine hypertension can be significantly antagonized or even reversed by IV injection of naloxone. IC injection of both bestatin and phosphoramidon did not affect the BP response to either acetylcholine or catecholamines. It is concluded that bestatin and phosphoramidon, injected into the carotid artery, inhibit the activity of aminopeptidase and "enkephalinase", thus producing an accumulation of enkephalins in the central nervous system. These enkephalins activate opioidergic receptors in the brain, but concomitantly produce a depression of the cholinergic-adrenergic interaction in the central nervous system, which is known to be a prerequisite for the hypertensive response to physostigmine in the rat.