Serotonin receptor agonists in the acute treatment of migraine. a review on their therapeutic potential

Migraine is an important socioeconomic burden and is ranked the sixth cause of years of life lost because of disability in the general population and the third cause of years of life lost in people younger than 50 years. The cornerstone of pharmacological treatment is represented by the acute therapy. The serotonin (5-hydroxytryptamine [5-HT]) receptor subtype 1B/1D agonists, called triptans, are nowadays the first-line acute therapy for patients who experience moderate-to-severe migraine attacks. Unfortunately, a high percentage of patients are not satisfied with this acute treatment, either for lack of response or side effects. Moreover, their mechanism of action based on vasoconstriction makes them unsuitable for patients with previous cardio- and cerebrovascular diseases and for those with uncontrolled hypertension. Since the introduction of triptans, no other acute drug class has passed all developmental stages. The research for a new drug lacking vasoconstrictive effects led to the development of lasmiditan, a highly selective 5-HT1F receptor agonist with minimized interactions with other 5-HT receptor subtypes. Lasmiditan is considered to be the first member of a new drug category, the neurally acting anti-migraine agent (NAAMA). Phase II and III trials had shown superiority compared to placebo and absence of typical triptan-associated adverse events (AEs). Most of the AEs were related to the central nervous system, depending on the high permeability through the blood-brain barrier and mild to moderate severity. The results of ongoing long-term Phase III trials will determine whether lasmiditan will become available in the market, and then active triptan comparator studies will assess patients’ preference. Future studies could then explore the safety during pregnancy and breastfeeding or the risk that overuse of lasmiditan leads to medication overuse headache

Prospective open-label study on the efficacy and tolerability of a combination of nutritional supplements in primary infertile patients with idiopathic astenoteratozoospermia

Aim of the study: To evaluate with an open-label study the efficacy and safety of a complex of nutritional supplements with antioxidant activity (L-carnitine, acetyl-L-carnitine, fructose, citric acid, selenium, coenzyme Q10, zinc, ascorbic acid, cyanocobalamin, folic acid) in primary infertile patients with idiopathic astenoteratozoospermia. Methods: The study was conducted in a population of 114 infertile men (96 completed the study) diagnosed with idiopathic astenoteratozoospermia since at least 18 months. Patients orally received a formulation (Proxeed - Sigma-Tau) containing L-carnitine 145 mg, acetyl-L-carnitine 64 mg, fructose 250 mg, citric acid 50 mg, selenium 50 mcg, coenzyme Q10 20 mg, zinc 10 mg, ascorbic acid 90 mg, cyanocobalamin 1.5 mcg, folic acid 200 mcg in combination once a day for 4 months. Results: At the end of study, the mean sperm progressive motility showed a statistically significant increase from 18.3 ± 3.8 to 42.1 ± 5.5. Sixteen patients achieved pregnancy during the study. No significant improvement were observed for sperm density and rate of morphologically normal forms. The treatment was well tolerated. Conclusions: Carnitines in association with others functional substances can improve the most important parameters of sperm quality

Migraine and cluster headache show impaired neurosteroids patterns

Background: Perturbation of neuronal excitability contributes to migraine. Neurosteroids modulate the activity of γ-aminobutyric acid A and N-methyl-d-aspartate receptors, and might be involved in the pathogenesis of migraine. Here, we measured plasma levels of four neurosteroids, i.e., allopregnanolone, epiallopregnanolone, dehydroepiandrosterone and deydroepiandrosterone sulfate, in patients affected by episodic migraine, chronic migraine, or cluster headache. Methods: Nineteen female patients affected by episodic migraine, 51 female patients affected by chronic migraine, and 18 male patients affected by cluster headache were recruited to the study. Sex- and age-matched healthy control subjects (31 females and 16 males) were also recruited. Patients were clinically characterized by using validated questionnaires. Plasma neurosteroid levels were measured by liquid chromatography-tandem mass spectrometry. Results: We found disease-specific changes in neurosteroid levels in our study groups. For example, allopregnanolone levels were significantly increased in episodic migraine and chronic migraine patients than in control subjects, whereas they were reduced in patients affected by cluster headache. Dehydroepiandrosterone and dehydroepiandrosterone sulfate levels were reduced in patients affected by chronic migraine, but did not change in patients affected by cluster headache. Conclusion: We have shown for the first time that large and disease-specific changes in circulating neurosteroid levels are associated with chronic headache disorders, raising the interesting possibility that fluctuations of neurosteroids at their site of action might shape the natural course of migraine and cluster headache. Whether the observed changes in neurosteroids are genetically determined or rather result from exposure to environmental or intrinsic stressors is unknown. This might also be matter for further investigation because stress is a known triggering factor for headache attacks in both migraineurs and cluster headache patients

L-carnitine fumarate, L-acetyl-carnitine and other components in male infertility: A pilot study of nutraceutics on sperm motility

The aim of this study was to evaluate any possible effect a combination of L-carnitine, fumarate, acetyl-Lcarnitine, fructose, citric acid, selenium, coenzime Q10, vitamin C, zinc, folic acid and vitamin B12 (Proxeed®) on sperm motility in a group of patients with unexplained asthenozoospermia. Thirty two patients received 1 sachet/day of Proxeed® for three months. Sperm parameters were studied before, during and after this treatment. Motility was also studied by the means of a computerized analysis (CASA system). The results of this study indicate that Proxeed® is able to increase sperm motility, both in a quantitative and qualitative manner. We conclude that oral administration of Proxeed® may improve sperm quality, at least in patients with idiopathic asthenozoospermia

Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

Compound useful for the prevention and treatment of accomodative asthenopia

descritto l'uso della L-carnitina, in combinazione con antiossidanti come la vitamina E ed elementi inorganici come manganese, zinco, sodio e potassio, per la preparazione di un integratore fisiologico o medicamento per uso oftalmico, per la prevenzione o il trattamento di astenopia accomodativa

Use of L-carnitine for the preparation of physiological supplement or medicament for ophthalmic use in the form of eye-drops”.

Uso della L-carnitina e / o di un suo sale per la preparazione di un Integratore oftalmico o medicamento per il trattamento dell’edema corneal

“Composition comprising as active ingredient a carnitine in combination with a solar filter, for the prevention and/or treatment of pathologies of the eye due to ultraviolet radiation”.

È descritta una composizione in forma di collirio o di pomata, comprendente come ingredienti attivi L-carnitina o un suo sale fisiologicamente accettabile, e 3-Hydroxykynurenine O-β-DL-glucoside, utile per prevenire o trattare patologie degli occhi causati da radiazioni ultraviolett