Structure-activity relationships of tricyclic antidepressants, with special reference to tianeptine.

Structure-activity relationships in the classical antidepressant (imipramine-like) series show a relative lack of specificities: Compounds should simply have a nucleus consisting of two phenyl rings and a third, seven-member central ring. This central ring may have one, several, or no heteroatoms, and it may or may not be saturated. The side chain may be attached to any one of the atoms of the central ring, but it must be short (two or three carbon atoms), and have a terminal amine group (secondary, tertiary, or included in a ring).

[Relation between the electronic structure of a series of 1,4-tetrahydro-oxazines and their p-D2, for the tryptaminergic receptor].

Certain features of the isopotential maps of morpholine derivatives seem to be related to their ability to bind with tryptaminergic receptors.

Dualist or pseudo-dualist interactions of mepyramine, diphenhydramine and eprozinol with histamine at H1-receptors.

The types of interaction of mepyramine (M), diphenhydramin: (D) and eprozinol (E), with histamine H1-receptors of guinea pig ileal and tracheal smooth muscle, were comparatively studied in vitro. According to the concentrations used, all three substances showed an apparent dualist mechanism of action on both preparations when histamine (dihydrochloride) was used as the agonist. The competitive component of this mechanism (at low concentrations) was characterized by the following pA2 values: 9.

Consequence of solubility alteration by salt effect on dissolution enhancement and biological response of a solid dispersion of an experimental antianginal drug.

Improvement of dissolution of a poorly water-soluble experimental antianginal drug has been obtained by solid dispersion preparation. Its solubility decreased with rising chloride ion concentration and biological responses in dogs varied with the gastrointestinal administration site. A correlation seemed to exist between the apparent solubility and the heart rate activity.