Characterization of [3 H]zetidoline binding to rat striatal membranes

Barone, Domenico; Assandri, Alessandro; Galliani, G.; Glässer, A.; Tarzia, Giorgio

doi:10.1111/j.2042-7158.1985.tb05036.x

Cited by 9 publications

(2 citation statements)

References 21 publications

(2 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the carboxamide group in orthopramides (e.g. 1) is replaced by an ureide function in zetidoline (4). As a consequence, the side chain in the latter is such that the distance between the basic azetidine N atom and the center of the phenyl ring can vary from 7-8 A in folded conformations to ca.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stereoelectronic study of zetidoline, a dopamine D2 receptor antagonist

Collin¹,

Evrard²,

Vercauteren³

et al. 1989

J. Med. Chem.

View full text Add to dashboard Cite

A combination of experimental and theoretical methods were used to investigate the stereoelectronic structure of zetidoline, a dopamine D2 receptor antagonist showing Na+-dependent binding. The solid-state conformation of zetidoline is characterized by synplanarity (coplanarity of the two rings with the chloro substituent and the carbonyl group on the same side). The side chain in the crystal adopts a folded conformation which places the azetidine nitrogen atom at about 8 A from the center of the aromatic ring. Quantum mechanical calculations indicate the synperiplanar and antiperiplanar conformations of the ring system to be of approximately equal energies. The molecular electrostatic potential of zetidoline in a nearly extended conformation shows a remarkable similarity with that of orthopramides (e.g. metoclopramide) and indolones (e.g. piquindone), i.e. two groups of drugs displaying the same D2 selectivity and Na+-dependent binding. We postulate that the close stereoelectronic similarity between zetidoline, orthopramides, and indolones accounts for their identical mechanism of action in the molecular level.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Among dopamine receptor antagonists, a number of compounds are known to act selectively on the subgroup of D2 receptors and to display a Na+-dependent binding.1-4 These compounds (see Scheme I) include orthopramides (e.g. metoclopramide (1), sulpiride, and tropapride), indolones (e.g. piquindone (2) and molindone (3)), and zetidoline (4).…”

mentioning

confidence: 99%

Stereoelectronic study of zetidoline, a dopamine D2 receptor antagonist

Collin¹,

Evrard²,

Vercauteren³

et al. 1989

J. Med. Chem.

View full text Add to dashboard Cite

show abstract

Structural requirements of Na+-dependent antidopaminergic agents: Tropapride, Piquindone, Zetidoline, and Metoclopramide Comparison with Na+-independent ligands

Collin

Vercauteren

Vanderveken

et al. 1989

J Computer-Aided Mol Des

View full text Add to dashboard Cite

Molecular graphic design coupled with PCILO and crystallographic results have been used to investigate the three-dimensional structure of Tropapride, Piquindone, Zetidoline, and Metoclopramide, four dopamine D-2 receptor antagonists showing Na+-dependent binding. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring and a carbonyl moiety, are similarly oriented in all the Na+-dependent drugs. Conversely, for Na+-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two pi-electron regions are systematically localized on the other side of the molecule: the first is a phenyl group while the second is a carbonyl function as in butyrophenones, a cyano group as in R48455, or a phenyl ring as in diphenylbutylpiperidines or tricyclics. The presence of a benzyl ring on this side in Tropapride might explain its weak extrapyramidal effects.

show abstract