Phthalane

Abstract: Relative reactivity of o-xylene, o-tolualdehyde, phthalide, and phthalane and the rate of phthalic anhydride formation from them have been determined. The main route of o-xylene oxidation to phthalic anhydride is due to the o-arrangement of methyl groups, proceeding through bicyclic products, such as dihydrobenzofuran (phthalane) and 3,4-benzofuran.

Abstract: The bicyclic phthalane and thiophthalane compounds, Lu 3-010 and Lu 5-003, although containing a ring system which is distinct from the ring system of tricyclic antidepressants, nonetheless, are approximately equipotent with tricyclic compounds in inhibiting the amine pump in adrenergic neurons. The Lu compounds require the presence of a phenyl ring on the bicyclic nucleus for full potency to be expressed. Molecular models of both of the enantiomers of the Lu compounds, when superimposed on a model of the ring system of desipramine, have their phenyl rings coincide closely with the phenyl rings of desipramine. With the enantiomers in these conformations the orientation of their propylamine side chains with respect to the phenyl rings is very similar to the orientation seen in desipramine. In addition, the Lu compounds have methyl groups on their bicyclic ring system which are involved in binding to the receptor. There are no analogous groups in the tricyclic system. The data suggest that the receptor for the amine pump in peripheral and central adrenergic nerve membranes, in addition to having primary sites for binding phenethylamine substrates, also has additional ancillary binding sites to which inhibitors attach themselves. Furthermore, the data also suggest that the number of ancillary sites is greater than is utilized by any one class of inhibitors. Although desipramine and the Lu compounds have binding sites in common, it appears that the Lu compounds are equipotent with desipramine only because they bind to an additional site.

Abstract: 1 Citalopram (Lu 10-171), a new bicyclic phthalane derivative, is an extremely potent inhibitor of neuronal serotonin (5-HT) uptake but has no effect on the uptake of noradrenaline (NA) and dopamine (DA) 2 Citalopram has no antagonistic activity towards DA, NA, 5-HT, histamine, gamma aminobutyric acid (GABA), acetylcholine, and morphine receptors In this way it clearly deviates from many old and new antidepressant drugs which have antagonistic effects towards some of these transmitters 3 In contrast to many tricyclic antidepressants citalopram is devoid of cardiotoxic effects, even when animals are exposed to concentrations far above the therapeutic level 4 In man citalopram is metabolized to compounds which are also potent 5-HT-uptake inhibitors without effect of NA uptake and which are found in lower concentrations than citalopram itself 5 In account of its extreme specificity as a 5-HT-uptake inhibitor citalopram should be considered as an experimental tool of the utmost importance In preliminary clinical experiments citalopram has shown a clear antidepressant effect This property together with the absence of troublesome anticholinergic adverse effects and cardiotoxic effects also make citalopram a most promising antidepressant drug