Photophysics and Photochemistry of Imipramine, Desimipramine, and Clomipramine in Several Solvents:  A Fluorescence, 266 nm Laser Flash, and Theoretical Study

Abstract

Imipramine (IPA) and its derivatives are used widely for the treatment of depression and other mental disorders. Although there are more than 20 FDA-approved antidepressant drugs, the search continues for better compounds with fewer deleterious side effects and higher efficacy. Over the past decade, several classes of antipsychotic drugs have been developed, which-in spite of their structural diversity-share an ability to modulate neurotransmission and to produce undesirable side effects. Phototoxicity is one of the most important side effects noted in treatment with tricyclic antidepressants (TCAs), but its mechanism has not yet been elucidated. To develop new knowledge regarding the relationship between the structure and the photophysics of these TCAs, we measured the photophysical properties of IPA, desimipramine (DIPA), and clomipramine (CIPA) in different solvents. The electronic configurations for the ground and the first excited singlet states were calculated using the AM1/RHF/CI and the AM1/RHF/HE semiempirical quantum theoretical methods, respectively. The ground-state properties are solvent-independent, while the emission maxima are red-shifted with increasing solvent polarity/polarizability. However, the fluorescence quantum yield is relatively low in all of the tested solvents (phif<0.02). The primary transient intermediates produced by 266 nm high-intensity laser photolysis are the solvated electron and the corresponding radical cation, with a negligible contribution of triplet-triplet absorption. The properties determined for the primary transients generated with a 266 nm laser flash are consistent with the photodamaging effects generated through a limited radical mechanism.

Photophysics and Photochemistry of z‐Chlorprothixene in Acetonitrile†

“…Fluorescence quantum yields of 0.0034 and 0.0022 were obtained for zCPTX and zCPTX–HCl, respectively. These low ϕ f values correspond very well with those reported for the promazines (10) and imipramines (6). As in the case of these structurally related drugs, fluorescence is not the major S 1 deactivation process for CPTX.…”

“…Then 10 μL of this mixture was injected at least three times into the HPLC to determine the quantity of remaining starting material. The quantum yield was then calculated as explained elsewhere (6). Briefly, the slope of the linear part of the concentration–time curve is equal to the rate of the zeroth‐order reaction ( k ), V is the irradiated volume (3 mL), I 0 is the lamp intensity at 313 nm, [zCPTX] 0 is the initial drug concentration, and α is the fraction of zCPTX that has reacted.…”

Mechanism of the oxidative degradation of dibenzoazepine derivatives via manganese(III) complexes in acidic phosphate media

“…In general, these results indicate that the reactivity of the TCA derivatives is similar in the reaction with the manganese(III) ion. The higher reactivity of the phenothiazine derivatives would be expected for simple electron transfer processes, because the presence of the sulfur atom decreases the reduction potential [37]. This phenomenon is not observed in the reaction with the manganese(III) ion, [24].…”

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

“…The authors considered that the PTL-HCl triplet state may be associated with the in vivo phototoxic effects of this drug [18]. In line with these experiments, the tricyclic antidepressants (TCAs) - Imipramine (IPA), desimipramine (DIPA) and clomipramine (CIPA) - photophysical properties were studied in different solvents [19]. It was shown that the primary transient intermediates produced by 266 nm high-intensity laser photolysis are the solvated electron and the corresponding radical cation, consistent with the results reported in [18].…”