The distribution of cinnarizine and its metabolites in the rat

Allewijn, F.

doi:10.1016/0024-3205(68)90106-9

Cited by 8 publications

(2 citation statements)

References 2 publications

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“…After oral administration, a maximum plasma concentration approaches in nearly 3 h with elimination half-life of 3 to 4 h ( Castaneda-Hernandez et al., 1993 ). Its six metabolites are known, which are produces via different of CYPs ( Allewijn, 1968 ). Although, cinnarizine has long been used in clinical practice with considerable tolerance but concerns has been raised for its association with drug-induced acute and chronic parkinsonism, linked to its ability to interact with dopamine receptors ( Teive et al., 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach

Mirza

Saadabadi

Vanmeert

et al. 2020

European Journal of Pharmaceutical Sciences

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Chemokine receptors are key regulators of cell migration in terms of immunity and inflammation. Among these, CCR5 and CXCR4 play pivotal roles in cancer metastasis and HIV-1 transmission and infection. They act as essential co-receptors for HIV and furnish a route to the cell entry. In particular, inhibition of either CCR5 or CXCR4 leads very often the virus to shift to a more virulent dual-tropic strain. Therefore, dual receptor inhibition might improve the therapeutic strategies against HIV. In this study, we aimed to discover selective CCR5, CXCR4, and dual CCR5/CXCR4 antagonists using both receptor- and ligand-based computational methods. We employed this approach to fully incorporate the interaction attributes of the binding pocket together with molecular dynamics (MD) simulations and binding free energy calculations. The best hits were evaluated for their anti-HIV-1 activity against CXCR4- and CCR5-specific NL4.3 and BaL strains. Moreover, the Ca 2+ mobilization assay was used to evaluate their antagonistic activity. From the 27 tested compounds, three were identified as inhibitors: compounds 27 (CCR5), 6 (CXCR4) and 3 (dual) with IC 50 values ranging from 10.64 to 64.56 μM. The binding mode analysis suggests that the active compounds form a salt bridge with the glutamates and π-stacking interactions with the aromatic side chains binding site residues of the respective co-receptor. The presented hierarchical virtual screening approach provides essential aspects in identifying potential antagonists in terms of selectivity against a specific co-receptor. The compounds having multiple heterocyclic nitrogen atoms proved to be relatively more specific towards CXCR4 inhibition as compared to CCR5. The identified compounds serve as a starting point for further development of HIV entry inhibitors through synthesis and quantitative structure-activity relationship studies.

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Section: Discussionmentioning

confidence: 99%

Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore‐based virtual screening approach

Mirza

Saadabadi

Vanmeert

et al. 2020

European Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Metabolism and excretion have been investigated in rats (Allewijn 1968, Soudijn & van Wijngaarden 1968, Janssen Pharmaceutica 1972a and in man (Janssen Pharmaceutica 1972b). Allewijn (1968) reported that after oral administration to rats, rapid absorption occurred from the gastrointestinal tract and peak tissue radioactivity levels were reached within 1 h in most tissues. Extensive metabolism occurred within 30 min of treatment and after 32 h the tissue levels were negligible.…”

Section: Pharmacokinetics and Dosagementioning

confidence: 99%