Search results for "Phenothiazines"
showing 10 items of 11 documents
Binding of several phenothiazine neuroleptics to a common binding site of alpha 1-acid glycoprotein, orosomucoid.
1983
The interaction of several phenothiazine neuroleptics with alpha 1-acid glycoprotein was investigated using circular dichroism and equilibrium dialysis techniques. For chlorpromazine only, one high-affinity binding site of the protein was found. The binding of the drug to this single site generated typical polyphasic extrinsic Cotton effects. Since several other phenothiazine neuroleptics gave qualitatively comparable extrinsic Cotton effects in the presence of alpha 1-acid glycoprotein and potently inhibited the binding of chlorpromazine to the single site, it was concluded that all phenothiazine derivatives investigated bound preferentially to only one common binding site of the alpha 1-a…
Characterization of basic drug–human serum protein interactions by capillary electrophoresis
2006
Drug-protein interactions are determining factors in the therapeutic, pharmacodynamic and toxicological drug properties. The affinity of drugs towards plasmatic proteins is apparently well established in bibliography. Albumin (HSA) especially binds neutral and negatively charged compounds; alpha(1)-acid glycoprotein (AGP) binds many cationic drugs, lipoproteins bind to nonionic and lipophilic drugs and some anionic drugs while globulins interact inappreciably with the majority of drugs. In this paper, the characterization of the interaction between cationic drugs, beta-blockers and phenotiazines towards HSA, AGP, and both HSA + AGP mixtures of proteins under physiological conditions by CE-f…
Ovicide-induced serosa degeneration and its impact on embryonic development in Manduca sexta (Insecta: Lepidoptera)
2003
Abstract Eggs of Manduca sexta treated with the ovicide Ov. 165049 turn orange, and the embryos later die. The orange pigmentation is at first confined to the serosa, and is accompanied by pathological changes of serosal cells. Lipid vesicles aggregate and spindle-shaped electron-lucent vesicles—normally forming a single layer below the apical cell surface—greatly accumulate. The mitochondria swell considerably, and their matrices become electron-lucent. Subsequently, the serosal cells develop additional features of necrosis. They form many autophagic vacuoles which contain mostly degradating mitochondria, but also segregated rough endoplasmic reticulum (rER) and glycogen granules. The whol…
Phenothiazines interfere with dopaminergic neurodegeneration in Caenorhabditis elegans models of Parkinson's disease
2010
Oxidative stress is involved in the pathogenesis of various neurodegenerative disorders, conventional antioxidant strategies have yet been of limited success. We have employed transgenic Caenorhabditis elegans expressing DsRed2 in dopaminergic neurons and CFP pan-neuronally, to characterize in larval and adult animals the effects of rotenone and 1-methyl-4-phenyl-pyridinium (MPP(+)) on the dopaminergic system. Investigating the antioxidant phenothiazine and different derived antipsychotic drugs, it was found that free phenothiazine exerted strong neuroprotection at the cellular level and resulted in a better performance in behavioral assays, whereas apomorphine and other dopamine agonists o…
Photoinduced chemiluminescence of pharmaceuticals
2005
Abstract A screening test for the forward development of chemiluminescence systems able to determine pharmaceutical compounds is reported. The test is based on the on-line photodegradation of the drugs by using a photoreactor consisting of 697 cm × 0.5 mm PTFE tubing helically coiled around an 8 W low-pressure mercury lamp. Photodegraded pharmaceuticals are detected by direct chemiluminescence of the resulting photofragments and their subsequent reaction with potassium permanganate in sulphuric acid medium as oxidant. The screening comprised 97 compounds with different molecular structures and relevant members of the most important families of pharmaceuticals are tested (amino acids, carbox…
The antioxidative, non-psychoactive tricyclic phenothiazine reduces brain damage after experimental traumatic brain injury in mice.
2014
Abstract Oxidative stress due to free radical formation is an important mechanism of secondary brain damage following traumatic brain injury (TBI). Phenothiazine has been found to be a strong antioxidant in eukaryotic cells in vitro and in invertebrates in vivo. The present study was designed to determine the neuroprotective potency of unsubstituted phenothiazine in a paradigm of acute brain injury. Thirty minutes after pneumatic, controlled cortical impact (CCI) injury, C57BI6 mice were randomly assigned to “low dose” (3 mg/kg, LD) or “high dose” (30 mg/kg, HD) s.c. phenothiazine or vehicle treatment. Brain lesion, neurofunctional impairment, body weight, and markers of cerebral inflammati…
Autonomous artificial nanomotor powered by sunlight
2006
Light excitation powers the reversible shuttling movement of the ring component of a rotaxane between two stations located at a 1.3-nm distance on its dumbbell-shaped component. The photoinduced shuttling movement, which occurs in solution, is based on a “four-stroke” synchronized sequence of electronic and nuclear processes. At room temperature the deactivation time of the high-energy charge-transfer state obtained by light excitation is ≈10 μs, and the time period required for the ring-displacement process is on the order of 100 μs. The rotaxane behaves as an autonomous linear motor and operates with a quantum efficiency up to ≈12%. The investigated system is a unique example of an artif…
Phenothiazine: the seven lives of pharmacology's first lead structure.
2011
Rooted in the early days of organic dye chemistry, the phenothiazine structure and its derivatives have since held a prominent place in pharmacology and biomedicine. Initially used for histochemical stains of plasmodia by Paul Ehrlich, anthelmintic and antibiotic properties of phenothiazines were globally exploited in the 1930s and 1940s. Clinical use of N-substituted phenothiazines as antihistaminics (1940s), sedatives and antipsychotics (1950s) followed and continues to this day. Recently, interest in these structures has re-emerged for a variety of fascinating features in relation to neurodegenerative disease, spearheaded by the unique redox chemistry of phenothiazine--arguably the most …
Increased acidophilia of eosinophil granules after EDTA treatment
1986
The acidophilic reaction of eosinophil leucocyte granules from human, pig and horse blood smears was investigated by using May-Grünwald-Giemsa staining after previous treatment with EDTA and sodium citrate solutions. The same peak at 530 nm, but absorption values considerably higher than those of controls, were found in eosinophil granules after application of chelating agents, indicating that removal of metal cations could unmask basic groups in these structures.
Multidrug resistance reverting activity and antitumor profile of new phenothiazine derivatives
2008
Abstract A series of easily affordable phenothiazine derivatives bearing a rigid but-2-ynyl amino side chain were synthesized and tested to evaluate the MDR reverting activity and full antitumor profile. Some compounds endowed with remarkable MDR reverting effect were identified, and the most active one ( 6c ) was shown to increase doxorubicin retention in multidrug resistant cells, suggesting a direct interaction with P-glycoprotein. Furthermore, a broad range of cellular activities were observed for different compounds. In particular, the ability of some derivatives to induce antiproliferative effects on resistant cell lines and to interfere with the G 1 phase of the cell cycle, a phase u…