Cyamemazine Research Articles

Photobehavior of the antipsychotic drug cyamemazine in a supramolecular gel protective environment

In this work, a molecular hydrogel made of gelator (S)-4-((3-methyl-1-(nonylamino)-1-oxobutan-2-yl)amino)-4-oxobutanoic acid (SVN) has been employed as soft container to modify the photochemical and photophysical behavior of the antipsychotic drug cyamemazine (CMZ). The interaction of CMZ with the gel network has been evidenced by fluorescence spectroscopy through a hypsochromic shift of the emission band (from λmax = 521 nm in solution to λmax = 511 nm in the gel) and an increase of the fluorescence lifetime (5.6 ns in PBS vs. 7.2 ns in the gel). In the laser flash photolysis experiments on CMZ/SVN systems, the CMZ triplet excited state (3CMZ*), monitored at λ = 320 nm, has been more efficiently generated and became much longer-lived than in solution (2.7 μs vs. 0.7 μs); besides, photochemical ionization leading to the radical cation CMZ+• was disfavored. In the steady-state experiments, photooxidation of CMZ to afford the N,S-dioxide derivative CMZ-SONO has been retarded in the gel, which provides a more lipophilic and constrained microenvironment. Both the photophysical properties and the photoreactivity are in agreement with CMZ located in a less polar domain when entrapped in the supramolecular gel, as result of the interaction of the drug with the fibers of the supramolecular SVN gel.

Development and validation of Novel UV-Spectrophotometric method for estimation of Cyamemazine Tartarate for simple, novel, rapid and cost effective analysis

Simple, novel, rapid and cost effective UV-spectrop hotometric method has been developed and validated for estimation of CYMT in bulk and tablet formulation. CYMT is a Phenothiazine derivative fr om the class of typical antipsychotic and a new drug for t he treatment of Schizophrenia. As no analytical met hod was seen in literature for determination of CYMT; we re port here, development and validation of simple, no vel UVspectrophotometric method for analysis of CYMT. Drug was found to be soluble in water and was stable f or more than 72 h in same solvent when tested for benc h top stability; being ideal solvent, spectrophotom etric studies were carried out using distilled water and detection as well as quantitation was performed at wavelength maximum of 267.21 nm. Linearity curve for developed method was generated by measuring absorbance at specified wavelength maximum and plotting it against concentration. The method followed linearity in r ange of 2 - 12 µg/mL with a correlation coefficient of 0.999. The m ean recovery of 98.97 reflects accuracy for developed method and the method precision was found to be well within acceptable limits. The developed method was tested and validated for various paramet ers as per USP requirements and recent ICH guidelines (addendum 2005). The present UV-spectrophotometric estimation for CYMT was proved to be statistically accurate, precise, and sensitive. The applicability of method can be extended towards rapid routine determination of drug in bulk and pharmaceutical fo rmulations and it has the unique importance of bein g first and simple UV-Spectrophotometric analytical method for the determination of CYMT in bulk and in pharmaceutical formulation

Retarded photooxidation of cyamemazine in biomimetic microenvironments.

Cyamemazine (CMZ) is a neuroleptic drug that mediates cutaneous phototoxicity in humans. Here, the photobehavior of CMZ has been examined within α1 -acid glycoproteins, β- and γ-cyclodextrins and SDS micelles. In all these microenvironments, CMZ emission was enhanced and blue-shifted, and its lifetime was longer. Irradiation of the entrapped drug at 355 nm, under air; led to the N,S-dioxide. Within glycoproteins or SDS micelles the reaction was clearly slower than in phosphate buffered solution (PBS); protection by cyclodextrins was less marked. Transient absorption spectroscopy in PBS revealed formation of the triplet state ((3)CMZ*) and the radical cation (CMZ(+•)). Upon addition of glycoprotein, the contribution of CMZ(+•) became negligible, whereas (3)CMZ* dominated the spectra; in addition, the triplet lifetime became considerably longer. In cyclodextrins, this occurred to a lower extent. In all microheterogeneous systems, quenching by oxygen was slower than in solution; this was most remarkable inside glycoproteins. The highest protection from photooxidation was achieved inside SDS micelles. The results are consistent with photooxidation of CMZ through photoionization and subsequent trapping of the resulting radical cation by oxygen. This reaction is extremely sensitive to the medium and constitutes an appropriate probe for localization of the drug within a variety of biological compartments.

Primary steps of the photochemical reactions of 2-cyano-10-(3-[dimethylamino, N-oxide]-2-methylpropyl)-5-oxide-phenothiazine, the photoproduct of cyamemazine, a phototoxic neuroleptic: comparison with the sulfoxide

The UVA-absorbing photoproduct resulting from the oxidation of the sulfur atom and of the side chain nitrogen of the phototoxic drug cyamemazine (CMZ) (2-cyano-10-(3-[dimethylamino]-2 methylpropyl)-phenothiazine) is a potent photodynamic photosensitizer. The photophysical and photochemical properties of this photoproduct (P) (2-cyano-10-(3-[dimethylamino, N-oxide]-2-methylpropyl)-5-oxide-phenothiazine)) have been investigated in neutral buffered aqueous solutions and in ethanol and compared to those of the sulfoxide (S) (2-cyano-10-(3-[dimethylamino]-2 methylpropyl)-5-oxide-phenothiazine), a CMZ oxidation product of cells. The fluorescence quantum yield (PhiF) of P is 0.25 and 0.21 in pH 7 phosphate buffer and ethanol, respectively. By contrast, S (PhiF = 0.14 in buffer) is practically unfluorescent in alcohol. In buffer, the fluorescence lifetimes of P and S are 10.5 and 11.8 ns, respectively. The transient absorbance of the first excited triplet state (3P1) with a characteristic absorption band peaking at 660 nm (epsilon = 5,300 M(-1) cm(-1)) has been observed by 355 nm laser flash spectroscopy of deaerated phosphate buffer or ethanol solutions. In buffer, the 3P1 lifetime is 0.5 micros. The energy transfer which occurs from the 3P1 to naproxen suggests that the 3P1 energy is greater than 62 kcal mol(-1). Triplet quenching by dioxygen occurs at rate 2.3 x 10(9) M(-1) s(-1). With the triplet benzophenone as actinometer, the 3P1 formation quantum yield is found to be 0. 40 in buffer. The 3P1 state is quenched by ethanol and 2-propanol with bimolecular reaction rate constants of 1.6 and 2.4 x 10(6) M(-1) s(-1), respectively. In buffer, P and S triplet states react with tryptophan, indole and cysteine at rate constants of the order of 10(9) M(-1) s(-1) for Trp and indole and 10(8) M(-1) s(-1) for Cys.

Contrasting action of flavonoids on phototoxic effects induced in human skin fibroblasts by UVA alone or UVA plus cyamemazine, a phototoxic neuroleptic

The potential protective effects of the flavanol catechin, the flavonol quercetin, the flavones, luteolin and rutin, and the isoflavones, genistein and daidzein, against the photo-oxidative stress induced by ultraviolet A radiation (UVA) and by phototoxic reactions resulting from the interaction of UVA with drugs and chemicals, has been assessed with cultured human skin fibroblasts. Lipid peroxidation and cell death have been chosen as model photobiological damage induced by UVA alone or photosensitized by cyamemazine (CMZ) and its photoproduct possessing phototoxic properties. Contrasting effects of flavonoids are observed. The flavanol, the flavonol and the flavones may protect against lipid peroxidation and cell death induced by 30 J cm(-2) of UVA alone or CMZ plus 10 J cm(-2) UVA. On the other hand, an amplification of the photodamage may be observed with isoflavones. A concentration-dependence study demonstrates that among the protective flavonoids, quercetin is the most efficient. The very effective protection brought by quercetin may result from its ability to scavenge reactive oxygen species produced by the photo-oxidative stress. However, the modification of membrane properties and the alteration of the lysosomal function by quercetin may not be neglected in these protective effects. The amplification of the photodamage by isoflavones is in sharp contrast with previous literature data demonstrating photoprotection by genistein. As a consequence, it may be concluded that an eventual antioxidant action of genistein may strongly depend on cells and photosensitizers. Furthermore such contrasting pro-versus anti-oxidant effects have to be taken into account when using flavonoid mixtures of plant extracts.

Primary Photochemical Processes of the Phototoxic Neuroleptic Cyamemazine: A Study by Laser Flash Photolysis and Steady‐state Irradiation¶

AbstractThe photophysical and photochemical properties of the UV‐A‐absorbing phototoxic drug cyamemazine (CMZ) (2‐cyano‐10‐(3‐[dimethylamino]‐2‐methyl‐propyl)‐phenothiazine) have been investigated in neutral buffered aqueous solutions. The transient absorbances of the hydrated electrons, of the first excited triplet state (3CMZ*) with a characteristic absorption band peaking at 420 nm and of the radical cation (•CMZ+) (maximum absorbance at 500 nm) have been observed by 355 nm laser flash spectroscopy of deaerated solutions. All these transient species are formed by monophotonic processes and react with oxygen. Bimolecular reaction rate constants of •CMZ+ and 3CMZ* with O2 are 2 × 107M−1 s−1 and 4 × 109M−1 s−1, respectively. The 3CMZ* reacts only sluggishly (reaction rate constant, 9 × 106M−1 s−1) with tryptophan chosen as a Type‐I photodynamic substrate. Steady‐state irradiations with 365 nm light demonstrate that CMZ is rapidly photolyzed (quantum yield, 0.04) in O2‐saturated solutions leading to oxidation of the sulfur atom and of the side‐chain nitrogen of CMZ. This photoproduct (2‐cyano‐10‐(3‐[dimethylamino, N‐oxide]‐2‐methyl‐propyl)‐5‐oxide‐pheno‐thiazine), is a good Type‐I and Type‐II photodynamic photosensitizer producing singlet oxygen in high yield (‐0.45) and could play a major role in the phototoxicity of CMZ.

Primary Photochemical Processes of the Phototoxic Neuroleptic Cyamemazine: A Study by Laser Flash Photolysis and Steady-state Irradiation¶

The photophysical and photochemical properties of the UV-A-absorbing phototoxic drug cyamemazine (CMZ) (2-cyano-10-(3-[dimethylamino]-2-methyl-propyl)-phenothiazine) have been investigated in neutral buffered aqueous solutions. The transient absorbances of the hydrated electrons, of the first excited triplet state (3CMZ*) with a characteristic absorption band peaking at 420 nm and of the radical cation (*CMZ+) (maximum absorbance at 500 nm) have been observed by 355 nm laser flash spectroscopy of deaerated solutions. All these transient species are formed by monophotonic processes and react with oxygen. Bimolecular reaction rate constants of *CMZ+ and 3CMZ* with O2 are 2 x 10(7) M(-1) s(-1) and 4 x 10(9) M(-1) s(-1), respectively. The 3CMZ* reacts only sluggishly (reaction rate constant, 9 x 10(6) M(-1) s(-1)) with tryptophan chosen as a Type-I photodynamic substrate. Steady-state irradiations with 365 nm light demonstrate that CMZ is rapidly photolyzed (quantum yield, 0.04) in O2-saturated solutions leading to oxidation of the sulfur atom and of the side-chain nitrogen of CMZ. This photoproduct (2-cyano-10-(3-[dimethylamino, N-oxide]-2-methyl-propyl)-5-oxide-phenothiazine), is a good Type-I and Type-II photodynamic photosensitizer producing singlet oxygen in high yield (approximately 0.45) and could play a major role in the phototoxicity of CMZ.