Administration of AMP soon after inoculation of mice with herpes simplex virus type 1 inhibited development of virus-induced lesions and appeared to prevent establishment of virus latency. These effects were dependent on both the AMP dose and the time of AMP administration. Regression of herpes simplex virus type 1-induced lesions was also accelerated significantly by AMP treatment in a timeand dose-dependent manner.The capacity of AMP to prevent both primary and recurrent herpes simplex virus type 1 (HSV-1) infections resulting from inoculation of mouse ear pinnae has been previously reported (1). Here we report the results of therapeutic trials carried out in the same animal model system. These investigations were prompted by several reports indicating possible antiviral activities inherent in adenosine or AMP (5, 10-12), as well as by a growing list of reported pharmacological and physiological effects of adenosine and AMP (2-4, 6, 9).The mouse ear pinnae model of Hill et al. (7,8) A multiple-dose treatment regimen (four doses over a 24-h period) was used to determine the minimum dose required to completely inhibit the formation of primary lesions. AMP (Sigma Chemical Co., St. Louis, Mo.) was dissolved in phosphate-buffered saline (pH 7.4) just before use and administered intraperitoneally. Nine groups of mice received AMP at 1, 6, 12, and 24 h after inoculation with HSV-1. The individual dose required to reduce the incidence of primary ear lesions by at least 50% was 2.0 mg/kg; the total dose was 8.0 mg/kg (Table 1). The minimum 100% inhibitory dose was 10 mg/kg, or a total of 40 mg/kg over 24 h.
Thirty-two adults were enrolled in a randomized, placebo-controlled double-blind trial of intramuscular injections of gel-sustained adenosine monophosphate (AMP) given three times a week for up to four weeks for acute herpes zoster. Adenosine monophosphate moderately reduced the pain soon after the start of treatment, decreased desquamation time, and promoted faster healing of the skin than placebo treatment. Adenosine monophosphate treatment reduced virus shedding and cleared the virus faster than in placebo-treated subjects. At the end of the initial four-week treatment period, 88% of AMP-treated patients were pain free, as opposed to only 43% in the placebo group. After four weeks, all patients who had not recovered from pain started receiving AMP treatment without breaking the code. All these patients recovered from pain within three weeks after initiation of treatment. No recurrence of pain or lesions was experienced from three to 18 months after the end of treatment. Adenosine monophosphate, a natural cellular metabolite, showed no side effects or toxicity during and after the treatment.
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