Several 4-alkyl-1-arylpiperazines that present a tetralin moiety on the terminal part of the side chain were synthesized in order to increase the selectivity on the 5-HT1A versus D-2, alpha 1, sigma, and other 5-HT receptors. Many changes have been effected on previous structures of type 3(1-aryl-4-[3-(1,2-dihydronaphthalen-4-yl)-n-propyl]piperazines). Several synthetic procedures were followed to obtain the final products, depending on the presence or absence of a double bond, as well as of a heteroatom on the side chain. In the first case versatile use of Grignard reaction was made, whereas in the second one usual synthetic ways were applied. Final compounds were evaluated for in vitro activity on dopamine D-1 and D-2, serotonin 5-HT1A, 5-HT1B, 5-HT1C, and 5-HT2, alpha 1 adrenergic, and sigma receptors by radioreceptor binding assay. For the 2-MeO-Ph, 2-pyridyl, and unsubstituted phenyl N-piperazine derivatives, low IC50 values (0.3 nM) on 5-HT1A receptors and high selectivity values were observed.

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The preparation of [(14) C]tribendimidine, a broad-spectrum anthelmintic agent related to amidantel, and its use during excretion and metabolism studies in the rat are described in this paper.

A deeper understanding of the pharmacokinetic and pharmacodynamic properties of a drug candidate is a pivotal component of drug discovery and development. Autoradiography is an excellent technique allowing exploiting the advantages of the use of radioisotopes in the drug disscovery field. The introduction of phosphor imaging technology has revolutionized the handling of drug distribution studies providing high‐resolution images. Specifically, quantitative whole‐body autoradioluminography is employed for preclinical study where the aim is to obtain information about the route of elimination and tissue distribution of a drug candidate. Autoradioluminography is also the technique of choice pursued to deal with all the issue that it is possible to encounter in all stage of drug development (ie, site‐specific drug localization and retention, drug‐drug interactions, penetration into specific target, specific tissue binding, crossing of brain blood barrier, and placental transfer). The purpose of this review is to give a picture of how autoradiography is employed in our laboratory as a key tool for advances in the assessment of the drug disposition and to validate new experimental models.