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We reviewed P300 and contingent negative variation (CNV) studies performed in migraine in order to identify their relevance in migraine and the role of neurophysiology in migraine. Publications available to us were completed by a Medline search. There is experimental and clinical evidence for loss of cognitive habituation in migraine which may serve as a specific diagnostic tool; therefore, we reviewed studies on migraine that analyzed habituation and lack of habituation by P300 and CNV, performing short-term habituation (STH) and long-term habituation (LTH). Finally, we described the two components of P300 (a and b) and of CNV (early and late wave) and the two abnormalities reported from the majority of studies on event-related potential in migraine: increased amplitude of average event-related potential and lack of habituation. These abnormalities are especially related to the early component characterizing orienting activity.

The pharmaco-toxicological profile of duloxetine, a novel SNRI antidepressant, is still not completely known; in particular, intoxication cases have been scarcely studied. Here a duloxetine overdose case, in combination with other antidepressants and benzodiazepines, is reported and the chemicalclinical correlations discussed; this is probably the first detailed report of such a case. The patient referred to have ingested nine tablets of Cymbalta† (more than 500 mg of duloxetine) and high amounts of four other drugs (venlafaxine, trazodone, sertraline and clonazepam). The patient was dozy and confused and some electrolyte imbalances were found. After gastrolavage, toxicological analyses revealed high plasma levels of duloxetine (384 ng/ml) and low levels of the other supposedly involved drugs. The overdose resulted to be not fatal and the outcome was relatively benign, also thanks to the fast emergency assistance. This case suggests that clinicians should be alerted to the possibility of toxic effects caused by simultaneous overdoses of duloxetine and other antidepressants and that caution should be used when prescribing more than one of these drugs to patients at risk of suicide.

Soymen GN is a new commercial preparation, containing soy extract and melatonin for the treatment of menopausal symptoms such as insomnia, hot flushes, tachycardia and osteoporosis. The commercial package contains two kinds of soft gelatin capsules: the “light” capsules for morning administration contain soybean extract (40 mg), while the “dark” capsules for evening administration contain soy extract (40 mg) and melatonin (5 mg). The main active compounds are the isoflavones, which are present both as aglycones and as glycosides: genistein, daidzein, glycitein, genistin and daidzin. These compounds are of particular interest for their possible estrogenic effects on the symptoms of menopause, in fact they have been used in therapy as a replacement to estrogen deficiency as a consequence of menopause. Melatonin is a hormone whose main function is the regulation of circadian rhythms. Thus, it can be helpful for the relief of insomnia and other sleep disturbances. The aim of this study is to develop a quality control system for the Soymen GN formulation. For this purpose, it is important to have access to reliable analytical methods for the determination of melatonin and of the main soy isoflavones, both aglycones and glycosides. Two original HPLC methods coupled to spectrophotometric and amperometric detection, respectively, have been developed for the quality control of Soymen GN capsules. UV detection is carried out at 260 nm, while amperometric detection is carried out at an oxidation potential of + 800 mV. The chromatographic separation is obtained using a reversed-phase C8 column as the stationary phase and a mixture of acetonitrile and an acidic phosphate buffer (30/70, v/v) as the mobile phase. A third analytical method based on micellar electrokinetic chromatography is currently undergoing validation. The BGE is composed of a 25 mM, pH 10.3 carbonate buffer, containing 55 mM SDS and 5% methanol. The analytes are quantitatively extracted from both “light” and “dark” capsules by agitation in a methanol/water mixture. From these preliminary results, all three methods seem to be promising for the quality control of the new formulation.

Introduction: Amphetamine (alpha-methylphenylethylamine) and its analogues such as methamphetamine (N,alpha-dimethylphenylethylamine) and MDMA (N,alpha-dimethyl-3,4-methylenedioxyphenylethylamine) are currently among the most well-known abuse drugs. They are used especially by young people as stimulants during the week-end (e.g. in discos), and are thus often referred to as "recreational drugs". Their mechanism of action is complex, but surely involves the release of catecholamines and serotonin from synaptic vesicles. Aim of this study is the development of a reliable analytical method for the simultaneous determination of amphetamine, methamphetamine and MDMA, and its application to the analysis of these compounds in human biological fluids, such as plasma and urine. Materials and Methods: Since the analytes show native fluorescence, liquid chromatography (HPLC) with fluorimetric detection was chosen for the purpose of separating and quantitating them. Separation was achieved on a C8 reversed-phase column using a phosphate buffer/acetonitrile (88:12) mixture (apparent pH = 2.8) as the mobile phase, flowing at 1 mL/min. Quinine was chosen as the Internal Standard (IS). Detection wavelengths were: lambda(exc) = 210 nm; lambda(em) = 300 nm for the analytes; lambda(exc) = 340 nm; lambda(em) = 420 nm for the IS. The sample pre-treatment procedure was carried out by means of solid-phase extraction (SPE) on hydrophilic-lipophilic balance cartridges. The cartridges were loaded with 250 µL of plasma or urine; the analytes were then eluted, dried and redissolved with 250 µL of mobile phase. Results: Under the described leading conditions, all analytes are baseline separated and detected within 13 minutes. Good linearity was obtained over different concentration ranges, according to the drug and the matrix. The sample pre-treatment procedure gave good extraction yields for all analytes, with mean recovery values ranging from 85 to 95% in plasma. Furthermore, the samples are devoid of interference from the biological matrices, thus good purification has been achieved. Conclusion: The method thus developed seems to be suitable for the determination of amphetamine, methamphetamine and MDMA in human plasma and urine.