Nociceptinergic system as potential target in Parkinson's disease.

Nociceptinergic system has become an important target for drug development since the identification of the "orphan", opioid-like-1 receptor and the isolation of its endogenous agonist nociceptin. Involvement of nociceptinergic system has been verified in a wide range of pathophysiological processes. A large number of nociceptinergic agonists and antagonists with peptide and non-peptide structures have been developed. Several non-peptide nociceptinergic antagonists have recently shown effective on different animal models of parkinsonism. Neuropharmacological background for antiparkinsonian effect of nociceptinergic antagonists, experimental models with high predictive value, nociceptinergic antagonists shown to have potential effect in Parkinson's disease are summarized. Medicinal chemistry data (logP and TPSA) of the NOP receptor antagonists which are found to be effective in animal models of Parkinson's disease are provided.

Prodrugs and active metabolites among antidepressive compounds.

Clinical effect of drugs is influenced by the composition of the pharmaceutical preparation but substantially by the fate of the drug in the body. Metabolism of the xenobiotic drug compounds may result in pharmacologically inactive metabolites, however, metabolites with higher pharmacological activity can also be produced. These active metabolites may have different pharmacokinetic properties than the parent drug. Co-existence of the parent drug and the active metabolite in the body may significantly modify the therapeutic effect. Knowledge-based system of pharmacokinetics and metabolism of the drugs has a high impact in understanding both the pharmacokinetic and the pharmacodynamic interactions. Cytochrome P450 isoenzymes taking part in the metabolic activity of the central nervous system is a developing area in metabolic studies. In the present study CYP isoenzymes with significant activity in the brain and the clinically important pharmacokinetic and metabolic data of antidepressive compounds are summarized.