Promazine

Promazine can be synthesized through various methods. One common method involves reacting diethylamine and epoxypropane to obtain 1-diethylamino-2-propanol, which is then reacted with chloride sulfoxide and toluene to obtain 1-diethylamino-2-chloropropane . This intermediate is then reacted with phenothiazine to obtain crude this compound, which is purified and salified with hydrochloric acid to obtain this compound hydrochloride . Industrial production methods often involve controlling raw material dosage, reaction temperature, and pH value to achieve high yield and purity .

Promazine undergoes various chemical reactions, including oxidation, reduction, and substitution. For example, it can be oxidized by sodium N-bromo-benzenesulfonamide in acidic medium to form this compound S-oxide . Common reagents used in these reactions include hydrochloric acid, methanol, and activated carbon . The major products formed from these reactions include this compound S-oxide and other oxidized derivatives .

Promazine is a medication with a range of applications, primarily in the fields of psychiatry and pharmacology. It is used for managing psychomotor agitation, agitation or restlessness in the elderly, and as an adjunct in treating psychotic symptoms . Additionally, research explores its potential as an antimicrobial agent .

Psychiatric Applications

Management of Psychomotor Agitation
this compound is effective in managing psychotic agitation due to its ability to reduce psychotic symptoms . Its benefits include ease of administration, rapid action, and improved patient compliance, especially in liquid form . Studies have demonstrated its efficacy in both short-term and long-term treatment scenarios .

Efficacy in Clinical Studies

• In a study of 259 patients with acute psychiatric syndromes, this compound effectively reduced agitation with minimal extrapyramidal side effects compared to chlorthis compound .
• Another study showed that 74% of hospitalized patients with psychotic agitation experienced marked improvement with liquid this compound, highlighting its rapid onset of action and ease of administration .
• A three-year study involving 180 chronic psychosis patients treated with various this compound formulations (tablets, liquid, injections) further supports its efficacy .

Mechanism of Action
this compound acts by inhibiting dopaminergic neurotransmission in a dose-dependent manner, reducing psychotic symptoms . It has a lower propensity to induce hyperprolactinemia compared to other antipsychotics, making it a preferred option in certain clinical scenarios . In vitro studies confirm that this compound can reversibly block dopamine-mediated responses, inhibiting dopamine activity .

Pharmacokinetics
this compound is efficiently absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 2–4 hours after oral administration . Its effects are typically noticeable within 20 minutes, making it valuable for rapid symptom control . The drug has a half-life of approximately 6 hours, requiring multiple daily doses to maintain symptom control .

Antimicrobial Research

Novel this compound Derivatives
A study aimed to synthesize a this compound derivative that would not cross the blood-brain barrier (BBB) but retain its antimicrobial properties . The novel compound, JBC 1847, exhibited increased in vitro antimicrobial activity against eight Gram-positive pathogens .

Limitations and Side Effects

• Phenothiazines, including this compound, can cause severe central nervous system side effects because they can permeate the BBB .
• In some in vivo studies, the administered dose needed to be reduced due to severe side effects observed in phenothiazine-treated animals .

Forensic Analysis

Lethal Intoxication
A forensic analysis of a suicide case in Poland involved a 63-year-old woman who used a lethal dose of this compound . The blood concentration of this compound was 8.47 mg/l, higher than the lowest lethal concentration of 5 mg/l . This case demonstrates that even drugs with a wide therapeutic index can be fatal at high doses .

Cognitive and Psychomotor Function

Effects on Cognitive Function
Promethazine (similar compound) produces significant impairments in cognitive and psychomotor function . Promethazine significantly reduced the CFF thresholds compared with placebo, fexofenadine and olopatadine . Promethazine significantly increased the response time compared with placebo, fexofenadine and olopatadine .

Interactions with SSRIs

Promazine exerts its effects by blocking a variety of receptors in the brain, particularly dopamine receptors . Dopamine is involved in transmitting signals between brain cells, and an excess amount of dopamine can cause over-stimulation of dopamine receptors . This compound acts as an antagonist at types 1, 2, and 4 dopamine receptors, 5-HT receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors .

Structural and Pharmacological Similarities

Promazine shares structural homology with other phenothiazines, such as chlorthis compound, differing primarily by the absence of a chlorine atom at the C2 position of the phenothiazine ring . This structural variation impacts potency and side-effect profiles. For example:

• Chlorthis compound requires lower doses (500 mg/day) than this compound (900 mg/day) to achieve comparable clinical effects in manic-depressive states .

Efficacy in Psychiatric Disorders

• Manic-Depressive States : In a study comparing 100 this compound-treated and 100 chlorthis compound-treated patients, both drugs showed comparable improvement rates. However, this compound required 30–400 mg higher daily doses depending on chronicity .
• Agitation and Psychosis : this compound demonstrated similar efficacy to chlorthis compound in reducing agitation but with a delayed onset (24–48 hours for oral administration) . Intramuscular administration eliminated this lag .

Pharmacokinetic Comparisons

Antiviral and Antimicrobial Activity

• SARS-CoV-2 : this compound showed weak in vitro inhibition (EC90 = 8.3 μM) but failed to reduce viral titers in mice, likely due to cytotoxicity .
• Staphylococcus aureus: Novel this compound derivatives exhibit antimicrobial activity but lower skin permeability (LogKp = -5.1) compared to standard agents .

Drug Interactions

• Tricyclic Antidepressants (TCAs) : Amitriptyline increases this compound plasma concentrations 3-fold and its metabolites 25-fold via competitive inhibition of metabolism .
• Benzodiazepines: Synergistic sedation is less pronounced with this compound than chlorthis compound due to lower histamine receptor affinity .

Promazine is a phenothiazine derivative primarily used as an antipsychotic medication. Its biological activity extends beyond its central nervous system effects, showing potential antimicrobial properties and varying efficacy against different pathogens. This article explores the biological activity of this compound, focusing on its pharmacological effects, antimicrobial potential, and case studies that highlight its applications and limitations.

Pharmacological Profile

This compound acts primarily as an antagonist of dopamine D2 receptors, which is a common mechanism among antipsychotic drugs. This action leads to its effectiveness in treating various psychiatric disorders, including schizophrenia and severe anxiety. However, the compound also interacts with other neurotransmitter systems, including serotonin and histamine receptors, contributing to its side effect profile.

Key Pharmacological Actions:

• Dopamine Receptor Antagonism : Reduces dopaminergic activity in the brain, alleviating psychotic symptoms.
• Antihistaminic Effects : Provides sedative properties, which can be beneficial in acute agitation.
• Anticholinergic Activity : May lead to side effects such as dry mouth and constipation.

Antimicrobial Activity

Recent studies have investigated the antimicrobial properties of this compound and its derivatives. A notable study synthesized a novel derivative of this compound that does not cross the blood-brain barrier (BBB) but retains antimicrobial properties. This derivative exhibited significant activity against several Gram-positive bacteria.

Antimicrobial Efficacy Data

In this study, JBC 1847 showed a significant reduction in bacterial growth compared to controls, indicating its potential as an antimicrobial agent without the severe CNS side effects associated with traditional this compound .

Case Studies

• Antimicrobial Efficacy Against Wound Infections :
  A study demonstrated that JBC 1847 significantly reduced infection rates in an in vivo model of wound infection caused by Staphylococcus aureus. The results indicated a P-value of less than 0.0001 when compared to control treatments, showcasing its effectiveness in clinical settings .
• Lack of Efficacy Against Viral Infections :
  Research evaluating this compound's effect on SARS-CoV replication found no significant antiviral activity. Despite initial hopes based on in vitro assays suggesting slight inhibition, this compound did not reduce viral loads in a mouse model . This highlights the limitations of this compound's efficacy against certain pathogens.

Safety and Side Effects

While this compound is effective for its intended psychiatric uses, it is associated with several side effects due to its action on multiple neurotransmitter systems. Common side effects include sedation, hypotension, and extrapyramidal symptoms. The modification of this compound into derivatives like JBC 1847 aims to reduce these adverse effects while maintaining therapeutic efficacy.

Q. Basic: What are the common methodological approaches for detecting and quantifying promazine in biological and pharmaceutical samples?

This compound detection typically employs electrochemical sensors or spectrophotometric methods. For example, a ZnO nanoparticle-modified carbon paste electrode demonstrated high sensitivity (detection limit: 0.34 μg/mL) for this compound in urine and pharmaceutical samples, with minimal interference from sugars and amino acids except ascorbic acid. Ascorbate oxidase can mitigate this interference . Spectrophotometric methods using Ce(IV) oxidation in sulfuric acid media (λ = 512 nm) achieve linearity (1–150 μg/mL, R² = 0.9997) and high throughput (23 samples/hour) via sequential injection analysis (SIA) optimized through a 3³ factorial design .

Q. Basic: How does this compound interact with transition metal ions, and what analytical techniques characterize these complexes?

This compound forms mononuclear complexes with Zn(II), Cd(II), and Hg(II) via its N-alkylamine side chain. These complexes exhibit square pyramidal geometry (sp³d hybridization) and are characterized using:

• UV-Vis spectroscopy : To confirm ligand-to-metal charge transfer.
• ¹H-NMR : To identify proton environments altered by metal coordination.
• Molar conductivity : Confirms 1:1 electrolyte behavior in DMF solutions.
• Magnetic susceptibility : Supports five-coordinate structures .

Q. Advanced: How can researchers resolve contradictions in this compound’s pharmacological efficacy across longitudinal studies?

Contradictions often arise from tolerance development. For instance, a study comparing this compound and chlordiazepoxide showed this compound’s potency decreased by 60% on day 2 and 34% on day 3 due to tolerance, while chlordiazepoxide maintained efficacy. To address such discrepancies:

• Control variables : Standardize dosing schedules and subject demographics.
• Mechanistic studies : Use skin resistance measurements to assess physiological adaptations (e.g., reduced sweating) .
• Statistical rigor : Apply dose-response modeling to distinguish drug-specific trends from experimental noise .

Q. Advanced: What experimental design strategies optimize this compound assay sensitivity and reproducibility?

A 3³ full factorial design optimizes parameters like acid concentration, oxidizer strength, and flow rate. For SIA-based this compound assays, optimal conditions include:

• Sulfuric acid : 1.0 × 10⁻⁴ M (avoids over-oxidation).
• Ce(IV) concentration : 0.01 M (balances reaction kinetics and signal stability).
• Flow rate : 10 μL/s (minimizes reagent waste while ensuring mixing efficiency).
  Validation via British Pharmacopoeia methods ensures accuracy (mean recovery: 98.2%) and precision (RSD <2.1%) .

Q. Advanced: How do researchers validate this compound’s pharmacological effects in behavioral models while controlling for confounding variables?

Key strategies include:

• Operant conditioning paradigms : Use free-operant avoidance tasks in animal models (e.g., pigeons) to isolate drug effects on stimulus-controlled behavior .
• Dose-response curves : Compare this compound with controls (e.g., chlorthis compound, d-amphetamine) to differentiate sedation from motor impairment.
• Cross-over designs : Administer this compound and placebo in randomized sequences to account for individual variability .

Q. Basic: What are the critical considerations for synthesizing and characterizing this compound derivatives?

• Purification : Use column chromatography to isolate intermediates.
• Structural validation : Combine elemental analysis (C, H, N, S) with IR spectroscopy to confirm functional groups (e.g., C–S stretching at 650–750 cm⁻¹).
• Stability testing : Assess hygroscopicity and photodegradation under accelerated conditions .

Q. Advanced: How can researchers address interference from biological matrices in this compound quantification?

• Matrix-matched calibration : Prepare standards in surrogate urine or serum to correct for matrix effects.
• Enzymatic interference removal : Use ascorbate oxidase to oxidize ascorbic acid in urine samples before electrochemical analysis .
• Standard addition method : Validate recovery rates (e.g., 97–103% in spiked pharmaceutical samples) to confirm method robustness .

Q. Basic: What pharmacokinetic parameters are critical for evaluating this compound’s therapeutic window?

• Half-life : Assessed via repeated blood/urine sampling using LC-MS or immunoassays.
• Protein binding : Equilibrium dialysis to measure free vs. bound this compound fractions.
• Metabolite profiling : Identify active metabolites (e.g., sulfoxides) via HPLC-MS/MS .

Q. Advanced: How do researchers analyze conflicting data on this compound’s hemodynamic effects in preclinical models?

Conflicts often stem from anesthesia interactions. For example, this compound-induced hypotension is exacerbated under regional anesthesia (e.g., pudendal block). Mitigation strategies include:

• Stratified dosing : Adjust this compound dosage based on anesthesia type.
• Hemodynamic monitoring : Use telemetry in conscious models to avoid anesthesia confounders .

Q. Advanced: What statistical frameworks are recommended for meta-analyses of this compound’s efficacy across heterogeneous studies?

• Random-effects models : Account for variability in study designs and populations.
• Sensitivity analysis : Exclude outliers (e.g., studies using non-validated assays).
• Publication bias assessment : Funnel plots and Egger’s regression to identify underreported negative results .