Promazine

Target of Action

Promazine, a phenothiazine antipsychotic, primarily targets a variety of receptors in the brain . Its primary targets include dopamine receptors (types 1, 2, and 4) , serotonin (5-HT) receptor types 2A and 2C , muscarinic receptors 1 through 5 , alpha(1)-receptors , and histamine H1-receptors . These receptors play crucial roles in transmitting signals between brain cells .

Mode of Action

This compound acts as an antagonist at its target receptors . This means it binds to these receptors and inhibits their activity. In particular, it blocks dopamine receptors, which are involved in transmitting signals between brain cells . When there is an excess amount of dopamine in the brain, it can cause over-stimulation of dopamine receptors . By blocking these receptors, this compound helps to regulate this signal transmission .

Biochemical Pathways

It is known that the drug’s antagonistic action on dopamine and serotonin receptors can affect various neural pathways and alter neurotransmission

Pharmacokinetics

It is known that this compound is a small molecule , which suggests it may be well-absorbed and distributed throughout the body. The metabolism of this compound is likely hepatic, as with other phenothiazines . More research is needed to fully understand the ADME properties of this compound and their impact on its bioavailability.

Result of Action

The molecular and cellular effects of this compound’s action primarily involve the regulation of neurotransmission in the brain. By blocking various receptors, this compound can help to regulate the transmission of signals between brain cells . This can help to manage conditions such as schizophrenia and psychomotor agitation .

Action Environment

The action, efficacy, and stability of this compound can be influenced by various environmental factors. For example, in veterinary medicine, this compound is used as a tranquilizer and its efficacy can be influenced by the animal’s health status and other concurrent medications . .

Biochemical Properties

Promazine acts by blocking a variety of receptors in the brain, particularly dopamine receptors . Dopamine is involved in transmitting signals between brain cells . When there is an excess amount of dopamine in the brain, it causes over-stimulation of dopamine receptors .

Cellular Effects

This compound has weak extrapyramidal and autonomic side effects which lead to its use in the elderly, for restless or psychotic patients .

Molecular Mechanism

The mechanism of action of this compound involves antagonism 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 .

Temporal Effects in Laboratory Settings

This compound is subject to considerable first-pass metabolism, resulting in significant plasma concentration variations between patients . It is highly toxic in overdose and can result in grand mal seizures, QT prolongation, and comas .

Dosage Effects in Animal Models

In large male animals, protrusion of the penis may occur . Excitement, restlessness, sweating, trembling, and, rarely, seizures and recumbency may occur .

Metabolic Pathways

Three types of metabolic mechanisms were characterized, including S-oxidation, aromatic hydroxylation, and N-dealkylation . The calculated results demonstrate that N14-demethylation is the most thermodynamically and kinetically favorable metabolic pathway of this compound, followed by S5-oxidation .

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 is similar to other phenothiazine derivatives such as chlorthis compound and promethazine . it has weaker antipsychotic effects compared to chlorthis compound . This compound and promethazine both bind to GDP-KRAS, but this compound has a higher affinity . Other similar compounds include cariprazine and quetiapine, which are atypical antipsychotics used to treat schizophrenia and bipolar disorder .

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.