Proguanil hydrochloride, an antimalarial prodrug, is metabolized to the active metabolite Cycloguanil (HY-12784). Proguanil hydrochloride is adihydrofolate reductase(DHFR) inhibitor^[1][2].

Proguanil per se has only weak antimalarial activityin vitro(IC₅₀=2.4-19 μM), and its effectiveness depends on the active metabolite Cycloguanil (IC₅₀=0.5-2.5 nM). The Cycloguanil is a dihydrofolate reductase (DHFR) inhibitor. The combination of Atovaquone and Proguanil is synergisticin vitro. Both drugs also have activity against gametocytes and pre-erythrocytic (hepatic) stages of malaria parasites^[1].
Proguanil acts as a biguanide rather than as its metabolite Cycloguanil (a parasite dihydrofolate reductase [DHFR] inhibitor) to enhance the Atovaquone effect. Proguanil-mediated enhancement is specific for Atovaquone, since the effects of other mitochondrial electron transport inhibitors, such as Myxothiazole and Antimycin, are not altered by inclusion of Proguanil^[2].
5-HT₃receptor responses are reversibly inhibited by Proguanil, the metabolite 4-chlorophenyl-1-biguanide (CPB) and the active metabolite Cycloguanil (CG), with an IC₅₀of 1.81, 1.48 and 4.36 μM, respectively^[3].

Proguanil (p.o.; 2.9 mg/kg body weight; daily for 5 days and 6 weeks respectively) shows mild degenerative changes for five days, while shows severe degenerative changes for six weeks in wistar strain albino rats^[4].
Serum testosterone level is significantly decreased for proguanil treatment rats^[4].
Administration of Malarone (Atovaquone and Proguanil) to experimentallyB. gibsoniinfected two dogs in chronic stage and three dogs in acute stage results in decrease in parasitemia, and clinical improvements are observed^[5].

290.19

C₁₁H₁₇Cl₂N₅

637-32-1

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