Diphenidol: Difference between revisions

{{Short description|Antiemetic and antivertigo drug}}

| verifiedrevid = 458630923

| IUPHAR_ligand = 7163

| C=21 | H=27 | N=1 | O=1

'''Diphenidol''' is a [[muscarinic antagonist]] employed as an [[antiemetic]] and as an anti[[Vertigo (medical)|vertigo]] agent. It is not marketed in the United States or Canada.

Although the mechanism of action of diphenidol on the [[vestibular system]] has not yet been elucidated, it exerts an [[anticholinergic]] effect due to interactions with [[Muscarinic receptor|mACh receptor]]s, particularly M₁, M₂, M₃ and M₄. Hence, its actions may take place at the vestibular nuclei, where a significant excitatory input is mediated by ACh receptors, and also at the vestibular periphery where mACh receptors are expressed at efferent synapses. A series of selective mACh-receptor antagonists based on the diphenidol molecule has been synthesized, but they have not yet been the subject of clinical trials.<ref>{{cite journal | vauthors = Soto E, Vega R | title = Neuropharmacology of vestibular system disorders | journal = Current Neuropharmacology | volume = 8 | issue = 1 | pages = 26–40 | date = March 2010 | pmid = 20808544 | pmc = 2866460 | doi = 10.2174/157015910790909511 }}</ref>

==Synthesis==

[[File:Diphenidol synthesis.svg|thumb|center|500px|Synthesis:<ref>Katz, Leon; Karger, Lawrence S. (1952). "The Mannich Reaction on α,α-Diphenylacetone". Journal of the American Chemical Society. 74 (16): 4085–4086. doi:10.1021/ja01136a034.</ref><ref>Gautier, J.A. et al, Bull. Soc. Chim. Fr., 1964, 2145.</ref><ref>Marxer, A. (1941). "Grignard-Reaktionen mit Halogen-alkyl-aminen". Helvetica Chimica Acta. 24 (2): 209E–225E. doi:10.1002/hlca.19410240225.</ref><ref>Vitale, Arturo A.; Doctorovich, F.; Sbarbati Nudelman, N. (1987). "One-pot synthesis of diarylalkylcarbinols and substituted derivatives through carbon monoxide insertion reactions into aryllithiums". Journal of Organometallic Chemistry. 332 (1-2): 9–18. doi:10.1016/0022-328X(87)85117-3.</ref> 10%:<ref>Schmidt, Andreas; Marchetti, Mauro; Eilbracht, Peter (2004). "Regioselective hydroaminomethylation of 1,1-diaryl-allyl-alcohols: a new access to 4,4-diarylbutylamines". Tetrahedron. 60 (50): 11487–11492. doi:10.1016/j.tet.2004.09.058.</ref> Patents:<ref>Marxer Adrian, Miescher Karl, {{US patent|2411664}} (1946 to Ciba Pharmaccutical Products I).</ref><ref>Barrett Paul Anthony & Wilkinson Samuel, GB683950 (1952 to Wellcome Found).</ref><ref>, BE620404 (1961 to SKF Labs).</ref>]]

Alkylation of [[1-Bromo-3-chloropropane]] [109-70-6] ('''1''') with [[piperidine]] ('''2''') gives 3-Piperidinopropyl chloride [1458-63-5] ('''3'''). The Grignard reaction of this intermediate with benzophenone [119-61-9] gives the benzhydrol and hence, Diphenidol ('''4''').

== References ==

{{reflist}}

[[Category:Antiemetics]]