Propiomazine

From Wikipedia, the free encyclopedia

Jump to: navigation, search
Propiomazine
Propiomazine.svg
Systematic (IUPAC) name
1-[10-(2-dimethylaminopropyl)-10H-phenothiazin-2-yl]propan-1-one
Clinical data
AHFS/Drugs.com Micromedex Detailed Consumer Information
Intramuscular, intravenous
Identifiers
362-29-8 YesY
N05CM06
PubChem CID 4940
DrugBank DB00777 YesY
ChemSpider 4771 YesY
UNII 242Z0PM79Y YesY
KEGG D02361 YesY
ChEBI CHEBI:8491 YesY
ChEMBL CHEMBL1201210 N
Chemical data
Formula C20H24N2OS
340.483 g/mol
 N (what is this?)  (verify)

Propiomazine (Largon, Propavan, Indorm, Serentin, Dorevane, Dorevan) is an antihistamine blocking H1 receptors. It is used to treat insomnia, and to produce sleepiness or drowsiness and to relieve anxiety before or during surgery or other procedures and in combination with analgetics also during labor. Propiomazine is a phenothiazine, but is not used as a neuroleptic because it does not block dopamine receptors well.

Mechanism of action[edit]

Propiomazine is an antagonist at types 1, 2, and 4 dopamine receptors, serotonin (5-HT) receptor types 2A and 2C, muscarinic receptors 1 through 5, alpha(1)-receptors, and histamine H1-receptors. Propiomazine's antipsychotic effect is due to antagonism at dopamine and serotonin type 2 receptors, with greater activity at serotonin 5-HT2 receptors than at dopamine type-2 receptors. This may explain the lack of extrapyramidal effects. Propiomazine does not appear to block dopamine within the tubero-infundibular tract, explaining the lower incidence of hyperprolactinemia than with typical antipsychotic agents or risperidone.

Side effects[edit]

Rare, serious side effects include convulsions (seizures); difficult or unusually fast breathing; fast or irregular heartbeat or pulse; fever (high); high or low blood pressure; loss of bladder control; muscle stiffness (severe); unusual increase in sweating; unusually pale skin; and unusual tiredness or weakness.

Drowsiness is a usual side effect.

Synthesis[edit]

Electrophilic aromatic substitution affords yet another route to ring-substituted phenothiazines.

Propiomazine synthesis:[1] Schmitt, FR addn. 71342 (addn. to FR 1176919  to Clin-Byla) IE 22637 .

Conversion of the parent phenothiazine to the propionamide (via the magnesium salt) serves as a protecting group for the amide as a means of allowing the para-directing effect of the sulfide to prevail. Acylation with propionyl chloride and aluminium chloride thus affords, after saponification of the amide, the ketone (4). This is then treated with phosgene to give 5, and this last esterified with 2-dimethylamino-1-propanol (N,N-dimethylalaninol) to yield the corresponding urethane (6). In an interesting reaction, pyrolysis of the urethane leads to extrusion of carbon dioxide and formation of 7, propiomazine.

See also[edit]

  • Propiopromazine (1497-CB).[2][3]

References[edit]

  1. ^ J. Schmitt, A. Halot, P. Comoy, M. Susquet, R. Fallard, and J. Boitard, Bull. Soc. Chim. France, 1474 (1957).
  2. ^ http://www.chemspider.com/Chemical-Structure.22768.html?rid=ea1d418a-1bbf-4b44-8ad7-4564af62ed93
  3. ^ J. Schmitt, J. Boitard, P. Comoy, A. Hallot, and M. Susquet, Bull. Soc. Chim. France, 938 (1957).