V. Bellotti

Bio: V. Bellotti is an academic researcher. The author has contributed to research in topics: High-performance liquid chromatography & Urine. The author has an hindex of 4, co-authored 5 publications receiving 175 citations.

Biosynthesis of salsolinol, a tetrahydroisoquinoline alkaloid, in healthy subjects.

Abstract: The R enantiomer of salsolinol was detected in the urine of two out of six healthy subjects, whereas 1,2-dehydrosalsolinol was present in the urine of all the subjects. (S)-salsolinol was never detected. Administration of Madopar for 7 days resulted in the presence of large amounts of (R)- and (S)-salsolinol in the urine of five out of the six subjects, the urinary excretion of 1,2-dehydrosalsolinol being generally not markedly increased.

Ratio of the R and S enantiomers of salsolinol in food and human urine

Abstract: Salsolinol is present in human fluids and tissues as well as in some foods and beverages. It was found previously that the R enantiomer of salsolinol predominates in human urine whereas the S enantiomer predominates in Port wine. In this study a new methodology for measuring the proportion of the R and S salsolinol enantiomers in dried banana and human urine is described. In dried banana, a food particularly rich in salsolinol, the R/S ratio was found to be very near to 1. In urine from additional healthy volunteers, the presence of only the R enantiomer was detected. The origin of urinary salsolinol and its enantiomeric composition are discussed with respect to exogenous salsolinol.

Urinary excretion of salsolinol enantiomers and 1,2-dehydrosalsolinol in patients with degenerative dementia

Abstract: The daily urinary excretion of total (R)- and (S)-salsolinol and 1,2-dehydrosalsolinol (free + sulfoconjugate) was measured in patients with degenerative dementia. (R)-Salsolinol was detectable in the urine of 5 out of 12 patients and 1,2-dehydrosalsolinol in the urine of 10 patients, whereas (S)-salsolinol was not detectable. The urinary excretion of 1,2-dehydrosalsolinol appears to be similar in demented and parkinsonian patients, suggesting that the biosynthesis of salsolinol precursors may be similar in the two groups.

The Pictet–Spengler Reaction in Nature and in Organic Chemistry

Abstract: Alkaloids are an important class of natural products that are widely distributed in nature and produced by a large variety of organisms. They have a wide spectrum of biological activity and for many years were used in folk medicine. These days, alkaloids also have numerous applications in medicine as therapeutic agents. The importance of these natural products in inspiring drug discovery programs is proven and, therefore, their continued synthesis is of significant interest. The condensation discovered by Pictet and Spengler is the most important method for the synthesis of alkaloid scaffolds. The power of this synthesis method has been convincingly proven in the construction of stereochemicaly and structurally complex alkaloids.

Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease.

Abstract: Current research in Parkinson’s disease (PD) focuses on symptomatic therapy and neuroprotective interventions. Drugs that have been used for symptomatic therapy are levodopa, usually combined with a peripheral decarboxylase inhibitor, synthetic dopamine receptor agonists, centrally-acting antimuscarinic drugs, amantadine, monoamine oxidase-B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors. Drugs for which there is at least some evidence for neuroprotective effect are certain dopamine agonists, amantadine and MAO-B inhibitors (selegiline). Levodopa remains the most effective drug for the treatment of PD. Several factors contribute to the complex clinical pharmacokinetics of levodopa: erratic absorption, short half-life, peripheral O-methylation and facilitated transport across the blood-brain barrier. In patients with response fluctuations to levodopa, the concentration-effect curve becomes steeper and shifts to the right compared with patients with stable response. Pharmacokinetic-pharmacodynamic modelling can affect decisions regarding therapeutic strategies. The dopamine agonists include ergot derivatives (bromocriptine, pergolide, lisuride and cabergoline), non-ergoline derivatives (pramipexole, ropinirole and piribedil) and apomorphine. Most dopamine agonists have their specific pharmacological profile. They are used in monotherapy and as an adjunct to levodopa in early and advanced PD. Few pharmacokinetic and pharmacodynamic data are available regarding centrally acting antimuscarinic drugs. They are characterised by rapid absorption after oral intake, large volume of distribution and low clearance relative to hepatic blood flow, with extensive metabolism. The mechanism of action of amantadine remains elusive. It is well absorbed and widely distributed. Since elimination is primarily by renal clearance, accumulation of the drug can occur in patients with renal dysfunction and dosage reduction must be envisaged. The COMT inhibitors entacapone and tolcapone dose-dependently inhibit the formation of the major metabolite of levodopa, 3-O-methyldopa, and improve the bioavailability and reduce the clearance of levodopa without significantly affecting its absorption. They are useful adjuncts to levodopa in patients with end-of-dose fluctuations. The MAO-B inhibitor selegiline may have a dual effect: reducing the catabolism of dopamine and limiting the formation of neurotoxic free radicals. The pharmacokinetics of selegiline are highly variable; it has low bioavailability and large volume of distribution. The oral clearance is many-fold higher than the hepatic blood flow and the drug is extensively metabolised into several metabolites, some of them being active. Despite the introduction of several new drugs to the antiparkinsonian armamentarium, no single best treatment exists for an individual patient with PD. Particularly in the advanced stage of the disease, treatment should be individually tailored.