Stereoisomers are molecules that are identical in atomic constitution and bonding. The biological properties may, however, differ significantly between two enantiomers (individual stereoisomers). JBC 1847, a phenothiazine derivative with strong antimicrobial activity against Gram-positive bacteria, exists in two enantiomers, S and R. Under standard chemical synthesis (S)-and (R)-JBC 1847 will be present in 50/50 amount (racemic). In this study, we have investigated the antimicrobial activity, the in vivo tolerance and therapeutic efficacy of purified (S)-JBC 1847. Compared to JBC 1847 racemic, the antimicrobial activity of (S)-JBC 1847 in vitro was in the same range or slightly increased, while the maximum tolerable concentration in vivo was five times higher for (S)-JBC 1847 (5 mg/kg versus 20 mg/kg bodyweight). Furthermore, the in vivo efficacy of (S)-JBC 1847 in a mouse peritonitis MRSA model was comparable to the activity of vancomycin. In conclusion, the antimicrobial activity and tolerance of a medical stereoisomeric compound may be significantly different using purified enantiomers compared with the racemic state.
UNASSIGNED: The online version contains supplementary material available at 10.1007/s12088-024-01309-3.

Nowadays, drug delivery systems (DDSs) are gaining more and more attention. Conducting polymers (CPs) are efficiently used for DDS construction as such systems can be used in therapy. In this research, a well-known CP, polypyrrole (PPy), was synthesized in the presence of the polysaccharide heparin (HEP) and chlorpromazine (CPZ) using sodium dodecyl sulfate (SDS) as electrolyte on a steel substrate. The obtained results demonstrate the successful incorporation of CPZ and HEP into the polymer matrix, with the deposited films maintaining stable electrochemical parameters across multiple doping/dedoping cycles. Surface roughness, estimated via AFM analysis, revealed a correlation with layer thickness-decreasing for thinner layers and increasing for thicker ones. Moreover, SEM images revealed a change in the morphology of PPy films when PPy is electropolymerized in the presence of CPZ and HEP, while FTIR confirmed the presence of CPZ and HEP within PPy. Due to its lower molecular mass compared to HEP, CPZ was readily integrated into the thin polymer matrix during deposition, with diffusion being unimpeded, as opposed to films with greater thickness. Finally, the resulting system exhibited the ability to release CPZ, enabling a dosing range of 10 mg to 20 mg per day, effectively covering the therapeutic concentration range.

Compared with conventional inorganic materials, organic electrodes are competitive candidates for secondary battery cathodes due to their resourcefulness, environmental friendliness, and cost-effectiveness. Much effort is devoted at the level of chemical structure, while ignoring the impact of molecular aggregation on battery behavior. Herein, this work designs a series of organic molecules with two electrochemically active phenothiazine groups linked by different lengths of alkyl chain to regulate molecular symmetry and crystallinity. The results emphasize the equally important role of molecular aggregation and chemical structure for battery performance. Among them, 2PTZ-C7H14|Li cell exhibits the most impressive cycle and rate performance. At the high rate of 50 C, it can still deliver a capacity of 63.4 mA h g-1 and 74.5% capacity retention after 10 000 cycles. Besides, the dropout voltage of 2PTZ-C9H18|Li cell is only 52 mV, which is among the lowest reported for lithium-organic batteries to the best of the author\'s knowledge.

The current review focuses on the effect of phenothiazine derivatives, tested in vitro, on necrosis and necroptosis, the latter constitutes one of the kinds of programmed cell death. Necroptosis is a necrotic and inflammatory type of programmed cell death. Phenothiazines are D1 and D2-like family receptor antagonists, which are used in the treatment of schizophrenia. Necroptosis begins from TNF-α, whose synthesis is stimulated by dopamine receptors, thus it can be concluded that phenothiazine derivatives may modulate necroptosis. We identified 19 papers reporting in vitro assays of necroptosis and necrosis in which phenothiazine derivatives, and both normal and cancer cell lines were used. Chlorpromazine, fluphenazine, levomepromazine, perphenazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate necroptosis and necrosis. The type of a drug, concentration and a cell line have an impact on the ultimate effect. Unfortunately, the authors confirmed both processes on the basis of TNF-α and ATP levels as well as the final steps of necrosis/necroptosis related to membrane permeability (PI staining, LDH release, and HMGB1 amount), which makes it impossible to understand the complete mechanism of phenothiazines impact on necroptosis and necrosis. Studies analyzing the effect of phenothiazines on RIPK1, RIPK3, or MLKL has not been performed yet. Only the analysis of the expression of those proteins as well as necrosis and necroptosis inhibitors can help us to comprehend how phenothiazine derivatives act, and how to improve their therapeutic potential.

The research of purely organic room-temperature phosphorescence (RTP) materials has drawn great attention for their wide potential applications. Besides single-component and host-guest doping systems, the self-doping with same molecule but different conformations in one state is also a possible way to construct RTP materials, regardless of its rare investigation. In this work, twenty-four phenothiazine derivatives with two distinct molecular conformations were designed and their RTP behaviors in different states were systematically studied, with the aim to deeply understand the self-doping effect on the corresponding RTP property. While the phenothiazine derivatives with quasi-axial (ax) conformation presented better RTP performance in aggregated state, the quasi-equatorial (eq) ones were better in isolated state. Accordingly, the much promoted RTP performance was achieved in the stimulated self-doping state with ax-conformer as host and eq-one as guest, demonstrating the significant influence of self-doping on RTP effect.

In this review, we summarized the current literature on the impact of phenothiazine derivatives on autophagy in vitro. Phenothiazines are antipsychotic drugs used in the treatment of schizophrenia, which is related to altered neurotransmission and dysregulation of neuronal autophagy. Thus, phenothiazine derivatives can impact autophagy. We identified 35 papers, where the use of the phenothiazines in the in vitro autophagy assays on normal and cancer cell lines, Caenorhabditis elegans, and zebrafish were discussed. Chlorpromazine, fluphenazine, mepazine, methotrimeprazine, perphenazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and novel derivatives can modulate autophagy. Stimulation of autophagy by phenothiazines may be either mammalian target of rapamycin (mTOR)-dependent or mTOR-independent. The final effect depends on the used concentration as well as the cell line. A further investigation of the mechanisms of autophagy regulation by phenothiazine derivatives is required to understand the biological actions and to increase the therapeutic potential of this class of drugs.

Phenothiazine and its derivatives have a number of properties that contribute to their wider practical use in the production of biologically active substances, drugs, dyes, etc. Therefore, the synthesis and study of new compounds is of great relevance. The aim of this work was to investigate the antioxidant activity of a number of new phenothiazine derivatives. The patterns of electroreduction of oxygen and its radicals in the presence of phenothiazine derivatives in aqueous ethanol media were studied by voltammetry. The influence of various factors on antioxidant activity was considered by the methods of experiment planning. The optimal conditions for the manifestation of the antioxidant activity of phenothiazine derivatives have been found, which seems to be relevant since it opens up new possibilities for their further use as complex preparations with antioxidant activity, including in psychiatric practice.

OBJECTIVE: To evaluate the effects of incremental doses of acepromazine on hemodynamics in isoflurane-anesthetized dogs.
METHODS: Prospective, experimental study.
METHODS: Healthy, adult, mixed-breed dogs (two male and four female) weighing 16.8 ± 5.1 kg (mean ± standard deviation).
METHODS: Dogs were anesthetized with propofol (7 mg kg-1) intravenously (IV) and isoflurane. Thermodilution and arterial catheters were placed for hemodynamic monitoring and arterial blood sampling for blood gas analysis. Baseline measurements were performed with stable expired concentration of isoflurane (Fe\'Iso) at 1.8%. Each dog was then administered four incremental acepromazine injections (10, 15, 25 and 50 μg kg-1) IV, and measurements were repeated 20 minutes after each acepromazine injection with Fe\'Iso decreased to 1.2%. The four acepromazine injections resulted in cumulative doses of 10, 25, 50 and 100 μg kg-1 (time points ACP10, ACP25, ACP50 and ACP100, respectively).
RESULTS: Compared with baseline, cardiac index (CI) increased significantly by 34%, whereas systemic vascular resistance index (SVRI) decreased by 25% at ACP50 and ACP100. Arterial oxygen content (CaO2) was significantly lower than baseline after all acepromazine injections (maximum decreases of 11%) and was lower at ACP50 and ACP100 than at ACP10. No significant change was found in heart rate, stroke index, oxygen delivery index and systolic, mean and diastolic blood pressures. Hypotension (mean arterial pressure < 60 mmHg) was observed in one dog at baseline, ACP10, ACP25 and ACP100, and in two dogs at ACP50.
CONCLUSIONS: Compared with isoflurane alone, anesthesia with acepromazine-isoflurane resulted in increased CI and decreased SVRI and CaO2 values. These effects were dose-related, being more pronounced at ACP50 and ACP100. Under the conditions of this study, acepromazine administration did not change blood pressure.

The aim of this study was to compare the sedative effects in cats administered acepromazine-nalbuphine and acepromazine-butorphanol, intramuscularly (IM) and intravenously (IV), and the occurrence of adverse cardiorespiratory effects.
Forty-six cats were randomly divided into four groups and administered acepromazine (0.05 mg/kg) combined with nalbuphine (0.5 mg/kg) or butorphanol (0.4 mg/kg), IV (ACP-NALIV and ACP-BUTIV groups, respectively) or IM (ACP-NALIM and ACP-BUTIM groups, respectively). Sedation scores, ease of intravenous catheter placement (simple descriptive scale [SDS] scores), physiologic variables, venous blood gases and the propofol dose required for anesthetic induction were recorded.
Mild sedation was observed in all groups approximately 30 mins after treatment administration (timepoint T1, prior to propofol administration). Sedation scores at T1 increased above baseline in all groups (P <0.05), but no significant difference was observed among groups. Dynamic interactive visual analogue scale sedation scores (range 0-100 mm) recorded at T1 were (median [interquartile range]): ACP-NALIM, 12 (10-12); ACP-NALIV, 11 (6-16); ACP-BUTIM, 11 (7-14); and ACP-BUTIV, 12 (7-19). Overall, SDS scores did not change from baseline at T1 and there was no significant difference among groups. The propofol dose did not differ among groups. Blood gases remained within the reference intervals for cats. Significant decreases from baseline were detected for all groups in systolic arterial pressure (SAP). Mean ± SD values at T1 were (mmHg): ACP-NALIM, 108 ± 13; ACP-NALIV, 102 ± 10; ACP-BUTIM, 97 ± 13; and ACP-BUTIV, 98 ± 21. Arterial hypotension (SAP <90 mmHg) was recorded at T1 in 0/11, 1/13, 4/11 and 5/11 cats in groups ACP-NALIM, ACP-NALIV, ACP-BUTIM and ACP-BUTIV, respectively, and was further exacerbated after the induction of anesthesia with propofol.
In healthy cats administered acepromazine-nalbuphine and acepromazine-butorphanol, IM and IV, the degree of sedation was mild regardless of the protocol and the route of administration. The main adverse effect observed was a reduction in arterial blood pressure.

A validated straightforward and sensitive spectrofluorimetric procedure was developed to assay trifluoperazine hydrochloride, promethazine hydrochloride, and perazine maleate. The procedure was dependent on oxidation of the investigated phenothiazines using a known excess of ammonium cerium sulfate as oxidizing agent and overseeing the fluorescence intensity of the resultant Ce3+ ion as the product of this reaction at λcx = 254 nm. and λem = 355 nm. Various parameters controlling the reaction were investigated and optimized. Linear calibration graphs were found in the general concentration range 5-30 ng/ml with a general correlation coefficient range 0.9994-0.9995. Limits of detection were 0.97, 0.70 and 0.56 ng/ml, whereas limits of quantification were 3.24, 2.12 and 1.89 ng/ml for trifluoperazine hydrochloride, promethazine hydrochloride and perazine maleate, respectively. The procedure was implemented successfully for analyses of the cited drugs in their trade dosage preparations such as tablets and syrups. The effect of possible interference from common excipients and their sulfoxide oxidized product was studied and the procedure showed good recovery of the drugs under study in their available dosage preparations. The possible effect of structure variation of the studied drugs on the experimental conditions and sensitivity observed with each one was also discussed.