62-97-5

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; Item No. 14486) 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.

Pranta,Schering,US,1952

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.

Prantal (Schering).

Spasmolytic

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.