Antiviral Effect of 3,4-Dihydro-1-Isoquinolineacetamide Hydrochloride in Experimental Human Rhinovirus Infection

Abstract

Double-blind trials were conducted in volunteers to evaluate the efficacy of the prophylactic 3,4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA) treatment against rhinovirus type 24 challenge. Ten men received a 7-day course of DIQA treatment and 11 men received a placebo. The intranasal viral challenge dose was 10 mean tissue culture infective doses. The oral administration of 1 g prechallenge and 2 g a day for 6 consecutive postchallenge days did not prevent the development of colds. Nine drug-treated men and 10 controls developed rhinovirus illness. However, the illnesses of the drug-treated men were mild. Rhinorrhea occurred less frequently and was more mild in the drug-treated group. The challenge virus was recovered from 80% of these subjects in both groups, but almost twice the number of challenge viruses were isolated from the controls than from the drug-treated men. The prophylactic DIQA therapy appears to suppress the cold syndrome and to reduce virus excretion, although its effect is marginal. Additional clinical trials are warranted to confirm the antirhinoviral effect of this drug.An antiviral compound, 3, 4-dihydro-1-isoquinolineacetamide hydrochloride (DIQA; Fig. 1) has been shown to be prophylactically effective in mice against infections produced by influenza (A/PR/8/34 and A/Japan/305/57), ECHO 9 (Coxsackie A23), herpes simplex, encephalomyocarditis (Columbia SK), St. Louis encephalitis, and West Nile viruses. The drug exhibited prophylactic and therapeutic activity against mumps infection in monkeys and effectively suppressed the development of herpes keratitis in rabbits, but the drug did not exert any effect on these viruses in tissue cultures.DIQA was active against Coxsackievirus Bi and vaccinia in tissue cultures, but was ineffective in vivo (1-3, 6).Two isoquinoline derivatives (UK 2054 and UK 2371) inhibited the in vitro growth of viruses belonging to the myxovirus and picornavirus groups (4). In experimentally induced ' Present address: Division of Infectious Diseases, Department of Medicine, Hahnemann Medical College & Hospital of Philadelphia, Philadelphia, Pa. 19102. types A and B influenza in man, the prophylactic treatment by UK 2371 (7) and by UK 2054 (5) significantly reduced the occurrence of the illness and suppressed the signs and symptoms. UK 2054, which showed an in vitro inhibitory action on rhinovirus type 9, failed to prevent experimental human infection of this virus (8).Although

Antirhinovirus activity of purine nucleoside analogs

“…No significant effects on rhinorrhea, clinical score, or virus excretion were noted whether the compounds were given intranasally (21,26,28,33,43) or orally (32,40 The fine editorial assistance of Christiane Callebaut is gratefully acknowledged.…”

“…Despite their potent and selective antiviral activity in vitro, the rhinovirus inhibitors that have so far been the subject of clinical studies, viz., enviroxime (21,26,28,33), 4',6-dichloroflavan (32), and some isoquinoline derivatives (40,43), have proven of little, if any, value in the prophylaxis or therapy of rhinovirus infections in volunteers. No significant effects on rhinorrhea, clinical score, or virus excretion were noted whether the compounds were given intranasally (21,26,28,33,43) or orally (32,40 The fine editorial assistance of Christiane Callebaut is gratefully acknowledged.…”

Experimental Antiviral Therapeutic Studies for Human Rhinovirus Infections

“…43 Advances in laboratory culture and genetic identification of virus species progressed gradually until the advent of highly sensitive molecular identification techniques including PCR, notably allowing the detection and classification of the RV-C species. 8 A large number of different strains have been used in experimental infection models to date, primarily from group A RVs: RV-1, 46 RV-2, 47 RV-9, 48 RV-16, [49][50][51][52][53] RV-24, 54 RV-23, 55 RV-29, 56 RV-32, 47 RV-39, 57 RV-44, 47,58 and Hank's strain. 59 RV-14, a group B rhinovirus has also been used in a single experimental infection 60 (Table 1).…”

“…This placebo controlled study demonstrated no benefit. 54 RV-23 Echinacea or placebo was given to healthy volunteers 14 days prior to, and for 5 days after, inoculation with RV-23. No significant difference in symptom scores or infections rates was detected.…”

Picornavirus inhibitors

“…Probably, this early step is the entry of virions into cells (Murphy and Glasgow, 1970). Clinical trials with DIQA have been conducted to prevent rhinovirus infection in volunteers (Togo et al, 1973a). Oral administration did not prevent the development of colds, but the symptoms in the treated group were milder than in the placebo-treated group (Togo et aL, 1973a).…”