Diphemanil is a quaternary ammonium anticholinergic agent. It induces relaxation of isolated guinea pig trachea strips precontracted with methacholine (EC50 = 0.12 nM). Diphemanil reverses increases in lung resistance and decreases in dynamic lung compliance induced by the non-selective acetylcholine receptor agonist carbachol (carbamoylcholine; ) in vagotomized cats (ED50s = 17.5 and 19.3 μg/kg, respectively). It reduces salivation induced by the muscarinic acetylcholine receptor agonist pilocarpine in mice when administered subcutaneously at doses ranging from 1.25 to 10 mg/kg.
Diphemanil Methosulfate is an anticholinergic agent; a synthetic quaternary ammonium compound with anitmuscarinic properties used in the treatment of Frey''s syndrome and is used as a parasympatholytic bronchodilator agent.
Bronchodilatator;Anticholinergic
ChEBI: The alkene resulting from the formal Wittig olefination of benzophenone and 1,1-dimethyl-4-bromopiperidinium methylsulfate. A quaternary ammonium anticholinergic, it binds muscarinic acetycholine receptors and thereby decreases secretory excretion of stoma
h acids, saliva and sweat, It is used topically in the treatment of hyperhidorsis (excessive sweating).
(A) Preparation of diphenyl-(N-Methyl-4-Piperidyl)carbinol: to a Grignard
solution prepared from 4.9 grams of magnesium, 100 cc of ether and 31.4
grams of dry
omobenzene is added 18.5 grams of 4-benzoyl-Nmethylpiperidine in 200 cc of dry ether. The reaction mixture is heated with
stirring for 4 hours on the steam bath and then decomposed. The organic
layer is separated and the aqueous layer extracted with benzene. The
combined organic extracts are concentrated and the residue, diphenyl-(Nmethyl-4-piperidyl)carbinol, recrystallized from benzene-petroleum ether, MP
130-131°C. The Grignard complex may also be decomposed with ice and
hydrochloric acid and the insoluble hydrochloride of the carbinol isolated
directly.
(B) Preparation of diphenyl-(N-Methyl-4-Piperidylidene)methane: the carbinol
can be dehydrated with 60% sulfuric acid. In general, to one part of the
carbinol there is added 10 parts of 60% sulfuric acid. The mixture after
heating for 6 hours is poured onto cracked ice, the solution made alkaline with
dilute sodium hydroxide and the oily basic layer extracted with ether. The
ether extracts after washing with water are dried over sodium sulfate, and after removing the ether, the residue is distilled in vacuo, MP 52°-53°C.
(C) Preparation of Final Product: The product from (B) is reacted with
dimethyl sulfate in benzene to give the final product, MP 196°-197°C.
Diphemanil methylsulfate,4-(diphenylmethylene)-1,1-dimethylpiperidiniummethylsulfate (Prantal), or diphemanil methylsulfate is apotent cholinergic blocking agent. In the usual dosagerange, it acts as an effective parasympatholytic by blockingnerve impulses at the parasympathetic ganglia, but it doesnot invoke a sympathetic ganglionic blockade. It is claimedto be highly specific in its action on those innervations thatactivate gastric secretion and GI motility. Although thisdrug can produce atropine-like side effects, they rarelyoccur at recommended doses. The highly specific nature ofits action on gastric functions makes the drug useful inthe treatment of peptic ulcer, and its lack of atropine-likeeffects makes its use much less distressing than other antispasmodicdrugs. In addition to its action in decreasinggastric hypermotility, diphemanil methylsulfate is valuablein hyperhidrosis in low doses (50 mg twice daily) or topically.The drug is not well absorbed from the GI tract,particularly in the presence of food, and should be administeredbetween meals. The methylsulfate salt was chosen asthe best, because the chloride is hygroscopic and the bromideand iodide ions have exhibited toxic manifestations inclinical use.
