Is the Anti-Psychotic, 10-(3-(Dimethylamino)propyl)phenothiazine (Promazine), a Dangerous Drug with Which to TreatSARS Infections? Efficacy of Promazine on SARS-CoV Replication in a Mouse Model

Authors

Dale L. Barnard, Utah State UniversityFollow
C. W. Day, Utah State UniversityFollow
K. Bailey, Utah State UniversityFollow
M. Heiner
R. Montgomery
L. Lauridsen
K. H. Jung, Utah State UniversityFollow
P. K. Chan
J. K. Li
R. W. Sidwell, Utah State University

Document Type

Article

Journal/Book Title/Conference

Barnard, D.L., Day, C.W., Bailey, K., Heiner, M., Montgomery, R., Lauridsen, L., Jung, KH.,Chan, P.K.-S. , Li, J.K-K., Sidwell, R.W. 2008. Is the Anti-Psychotic, 10-(3-(Dimethylamino)propyl)phenothiazine (Promazine), a Dangerous Drug with Which to TreatSARS Infections? Efficacy of Promazine on SARS-CoV Replication in a Mouse Model.Antiviral Res. 79:105-13. PMID: 18423639

Volume

79

Publication Date

2008

First Page

105

Last Page

113

Abstract

Phenothiazine and derivatives were tested for inhibition of SARS-CoV replication. Phenothiazine slightly inhibited SARS-CoV replication in a neutral red (NR) uptake assay. Adding a propylamino group to give promazine reduced virus yields (VYR assay) with an EC90 = 8.3 ± 2.8 μM, but without selectivity. Various substitutions in the basic phenothiazine structure did not promote efficacy. Phenazine ethosulfate was the most potent compound by VYR assay (EC90 = 6.1 ± 4.3 μM). All compounds were toxic (IC50 = 6.6–74.5 μM) except for phenoxathiin (IC50 = 858 ± 208 μM) and 10-(alpha-diethylamino-propionyl) phenothiazine·HCl (IC50 = 195 ± 71.2 μM). Consequently, none were selective inhibitors of SARS-CoV replication (SI values <1–3.3 μM). These data portended the poor efficacy of promazine in a SARS-CoV mouse lung replication model. Intraperitoneal treatment with promazine using a prophylactic (−4 h)/therapeutic regimen of 1, 10, or 50 mg/(kg day) did not reduce virus lung titers at day 3, yet prolonged virus replication to 14 days. Similar therapeutic promazine doses were not efficacious. Thus, promazine did not affect SARS-CoV replication in vitro or in vivo, nor were any other phenothiazines efficacious in reducing virus replication. Therefore, treating SARS infections with compounds like promazine is not warranted.

Comments

Antiviral Res. 79:105-13. PMID: 18423639

Recommended Citation

Barnard, D.L., Day, C.W., Bailey, K., Heiner, M., Montgomery, R., Lauridsen, L., Jung, KH., Chan, P.K.-S. , Li, J.K-K., Sidwell, R.W. 2008. Is the Anti-Psychotic, 10-(3- (Dimethylamino)propyl)phenothiazine (Promazine), a Dangerous Drug with Which to Treat SARS Infections? Efficacy of Promazine on SARS-CoV Replication in a Mouse Model. Antiviral Res. 79:105-13. PMID: 18423639