Guaiacol -- a new compound in the treatment of gastro-oesophageal reflux?

Abstract

SUMMARY The effects on the oesophagus of an aromatic oil, guaiacol, has been examined in a group of 20 patients with reflux oesophagitis and also normal volunteers. This agent produced a rapid and sustained rise in resting lower oesophageal sphincter pressures and the peristaltic pressures induced in response to swallowing liquids. This compound may prove useful in the treatment of patients with reflux oesophagitis and other disorders of oesophageal motility.Aromatic oils or substances containing them have been used as internal medicinal agents from the earliest times. The therapeutic aims have been numerous but probably the most frequent has been to produce the 'carminative' effect. Carminatives are agents which produce a sensation of abdominal warmth and relieve gastrointestinal distension when ingested orally, probably by increasing gut mucosal blood flow and acting as antispasmodics.1-3 Indeed, it may have been these properties which prompted Hippocrates (460-361 BC), for example, to use oil of rue as an antispasmodic, stimulant, and rubefacient in the treatment of childhood colic.Pharmacological studies performed on isolated preparations of mammalian smooth muscle, using known constituents of volatile oils and other chemically related agents, have demonstrated that many of these compounds decrease muscle tone and spontaneous contractility; properties which are characteristic of antispasmodics and spasmolytics.4 We have identified one aromatic oil, however, which increases spontaneous activity of isolated muscle strips in vitro and the canine colon in vivo. 5 6 We have further examined the efficacy of this compound in the human oesophagus in normal individuals and patients suffering from gastrooesophageal reflux complicated by oesophagitis. Diminution in oesophageal peristalsis and resting tone of the lower oesophageal sphincter (LOS) are believed to contribute to the pathophysiology of reflux oesophagitis and it is likely that a topically-

Guaiacol as a drug candidate for treating adult polyglucosan body disease

“…roasted coffee and vanilla. Medically, it has been used for treating respiratory diseases, cough, and reflux (14,15). The combination of the precedential usage of guaiacol in the clinic and the encouraging in vitro and in vivo results presented here anticipate a relatively uncomplicated transition of guaiacol to clinical settings.…”

“…Discovery of guaiacol as a therapeutic candidate for APBD. In our hands, guaiacol, initially used for treating respiratory and throat ailments (14,15), was discovered as a drug candidate for APBD by HTS of the 1,700-compound library of FDA-approved drugs (Supplemental File 1; supplemental material available online with this article; https://doi.org/10.1172/jci.insight.99694DS1). This HTS was performed in fibroblasts derived from APBD-modeling mice (GBE1 neo/-) (17), which are compound heterozygous, with a polymorphic allele and exon 7 deletion, in their GBE.…”

“…Guaiacola GYS inhibitor and a candidate for APBD therapy. Initially used for treating lung abscesses (14), guaiacol has been used to treat reflux esophagitis (15) and, in combination with codeine (Pulmo Bailly), or as a precursor to guaifenesin (Resyl Syrup), to treat cough. In this work, we show that guaiacol, discovered as a positive hit for PGB reduction in a high-throughput screening (HTS) campaign, is a potent, nontoxic inhibitor of GYS1 and GYS2.…”

Pharmacological Bases of the Medical Treatment of Gastroesophageal Reflux Disease

“…These include bromopride [Lazaro da Silva et al" 1983], clebropride [Vantrappen et al, 1985], alizapride [Cadranel et al, 1986], ciclizine [Brock-Utnc et al, 1977], metopimazine [Gossclin et al, 1981], guaiacol [Heatley et al. 1982] and actually pinaverium bromide, an antispasmodic compound [Marzio et al, 1984], The stimulatory effect of trimebutine on LES smooth muscle [Bel et al.…”