The Quinoxaline Derivative Caroverine in the Treatment of Sensorineural Smell Disorders: a Proof-of-Concept Study

Abstract

The treatment of non-conductive olfactory disorders is to a large extent an unsolved problem. This proof-of-concept study focused on possible effects of the N-methyl-D-aspartate (NMDA) antagonist caroverine. Potential mechanisms for the hypothesized effect included reduced feedback inhibition in the olfactory bulb as a consequence of NMDA antagonistic actions and antagonism of an excitotoxic action of glutamate. A total of 77 consecutive patients with non-conductive olfactory disorders were included in the study. Fifty-one patients received caroverine for 4 weeks (120 mg/day); 26 controls matched for age, gender and duration of olfactory loss were treated with zinc sulfate for the same length of time (400 mg/day). Olfactory sensitivity was evaluated before and after treatment. Testing included assessment of n-butanol odor threshold and odor identification. When compared to baseline, treatment with caroverine improved both odor thresholds (p = 0.005) and odor identification (p = 0.042) in anosmic patients. In hyposmic patients it significantly improved odor identification ability (p = 0.041). In contrast, zinc sulfate had no significant effect on olfactory function. These results indicate that caroverine appears to be effective for the treatment of non-conductive smell disorders.

The Effect of Olfactory Training Using Korean Version Odorants: A Preliminary Study

“…20,21) Numerous therapeutic strategies have been proposed, such as the use of strychnine, zinc, theophylline, lipoic acid, and caroverine. 3,8,9,[22][23][24][25][26][27] Although the effectiveness of most of these regimens is far from clear, the usefulness of corticosteroids in sensorineural dysfunction-related olfactory loss is established. This is supported by the observation that systemic steroids are helpful in sensorineural dysfunction-related olfactory loss.…”

“…Introduction and topical steroids. 5,6) Furthermore, repeated short-term exposure to odorants so-called olfactory training (OT), vitamin B, 7) caroverine, 8) alpha-lipoic acid, 9) minocycline, 10) and acupuncture 11) appears to be effective in improving olfaction.…”

What to propose to treat post-viral non-conductive smell disorder in COVID-19? - systematic review with meta-analysis

“…After the reading, six articles were excluded because their samples were composed of patients with obstructive nasal disease (table 1). However, of the 13 studies included in the qualitative analysis (table 2), ve studies were unique in their treatment [10,[21][22][23][24] and four did not have enough data for quantitative analysis (meta-analysis) [25][26][27][28]. Thus, four studies were selected for the meta-analysis involving 336 patients [29][30][31][32] (table 3).…”

“…Outcome measures were determined by symptom scores and objective methods of olfactory testingwith the Sni n`Sticks test as the most common test used in the studies. Ten studies compared the mean TDI score ("T" -threshold, "D"discrimination, "I" -identi cation) before and after drug treatment in NCSD (total of six drugs) [10,[21][22][23][24][25][26][27][28], while four compared the mean TDI score before and after olfactory training in NCSD [29][30][31][32] (table 3). Of the studies with drug treatment, ve were the only ones for the drug they proposed to analyze (oral caroverine, oral vitamin A, intranasal insulin, intravenous pentoxifylline and oral lipoic acid) [10,21-24] and four were on intranasal sodium citrate [26][27][28]; however, studies with sodium citrate did not provide su cient pre-and posttreatment data for meta-analysis.…”

Position paper on olfactory dysfunction

“…No improvement in smell loss Reden et al (295) Improvement following systemic and local corticosteroids; also improvement with systemic Vitamin B after 6 monthsv Quint et al (298) 2002 Prospective, controlled…”