Toxic Retinopathy Following Sparsomycin Therapy

Some Observations on the Macula of Pesticide Workers

“…The highest incidence of macular involvement is reported with chloroquine (1-20%) (Michelson, 1980) and phenothiazines (15%) (Alkemade, 1966). Other drugs reported to be associated with macular changes are sparsomycin (McFarlane et al, 1966), allopurinol (Pina, 1968), arsenic (Sattler, 1932) and indomethacin (Burns, 1966). The results of our study show that 19% of group II workers had macular changes, similar changes were present in 3% of control subjects.…”

Some Observations on the Macula of Pesticide Workers

“…The highest incidence of macular involvement is reported with chloroquine (1-20%) (Michelson, 1980) and phenothiazines (15%) (Alkemade, 1966). Other drugs reported to be associated with macular changes are sparsomycin (McFarlane et al, 1966), allopurinol (Pina, 1968), arsenic (Sattler, 1932) and indomethacin (Burns, 1966). The results of our study show that 19% of group II workers had macular changes, similar changes were present in 3% of control subjects.…”

Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo

“…The use of Sm was discontinued from a phase I clinical study because of a finding that, by daily doses of Sm, two out of five patients (with advanced carcinoma) developed ring scotoma after 13 days (total dose of 0.24 mg/kg) and 15 days (total dose of 0.15 mg/kg); this effect was later defined as Sm-related retinopathy [ 12 ]. Later identification by Ottenheijm et al [ 7 ] reported no observable pathological changes in the retinas of any animal treated with toxic doses of Sm and further suggested that Sm-related retinopathy was caused by a poor general condition of the patients and inappropriate drug schedules.…”

“…Sm binds primarily to the peptidyl (P) site and, because of the stabilization of the P-site/tRNA, the drug blocks the critical movement of tRNAs between the aminoacyl site and P-site, resulting in the inhibition of peptide bond formation and the inability of aminoacyl–tRNA to access the P-site [ 9 , 10 , 11 ]. Despite acute toxicity of Sm in mice [ 6 ] and Sm-related retinopathy in the phase I clinical study [ 12 ], an active testing program of the drug related to the protein biosynthesis machinery has continued [ 10 , 13 , 14 ]. Considering the effects of Sm on protein translation, the in vitro inhibitory activity of Sm against the most common and deadliest human malaria parasite, P. falciparum (3D7 and K1) [ 15 ], was evaluated.…”

Sparsomycin – a Review and Re-assessment

“…at up to 1 mg/day) against lung, cecum, and colon cancers in advanced patients was halted due to ocular toxicity (blurred vision) from the development of scotomas. 60,61 The additional biological significance of analogs of 1 became evident when it was shown that through coadministration, ethyl-deshydroxy-sparsomycin (60) at 10 mg/kg enhanced the anticancer activity of cisplatin with L1210 cells i.p. in mice 2.8-fold.…”

Some Observations on the Macula of Pesticide Workers

“…The highest incidence of macular involvement is reported with chloroquine (1-20%) (Michelson, 1980) and phenothiazines (15%) (Alkemade, 1966). Other drugs reported to be associated with macular changes are sparsomycin (McFarlane et al, 1966), allopurinol (Pina, 1968), arsenic (Sattler, 1932) and indomethacin (Burns, 1966). The results of our study show that 19% of group II workers had macular changes, similar changes were present in 3% of control subjects.…”

Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo

“…The use of Sm was discontinued from a phase I clinical study because of a finding that, by daily doses of Sm, two out of five patients (with advanced carcinoma) developed ring scotoma after 13 days (total dose of 0.24 mg/kg) and 15 days (total dose of 0.15 mg/kg); this effect was later defined as Sm-related retinopathy [ 12 ]. Later identification by Ottenheijm et al [ 7 ] reported no observable pathological changes in the retinas of any animal treated with toxic doses of Sm and further suggested that Sm-related retinopathy was caused by a poor general condition of the patients and inappropriate drug schedules.…”

“…Sm binds primarily to the peptidyl (P) site and, because of the stabilization of the P-site/tRNA, the drug blocks the critical movement of tRNAs between the aminoacyl site and P-site, resulting in the inhibition of peptide bond formation and the inability of aminoacyl–tRNA to access the P-site [ 9 , 10 , 11 ]. Despite acute toxicity of Sm in mice [ 6 ] and Sm-related retinopathy in the phase I clinical study [ 12 ], an active testing program of the drug related to the protein biosynthesis machinery has continued [ 10 , 13 , 14 ]. Considering the effects of Sm on protein translation, the in vitro inhibitory activity of Sm against the most common and deadliest human malaria parasite, P. falciparum (3D7 and K1) [ 15 ], was evaluated.…”

Sparsomycin – a Review and Re-assessment

“…at up to 1 mg/day) against lung, cecum, and colon cancers in advanced patients was halted due to ocular toxicity (blurred vision) from the development of scotomas. 60,61 The additional biological significance of analogs of 1 became evident when it was shown that through coadministration, ethyl-deshydroxy-sparsomycin (60) at 10 mg/kg enhanced the anticancer activity of cisplatin with L1210 cells i.p. in mice 2.8-fold.…”

Some Observations on the Macula of Pesticide Workers

“…The highest incidence of macular involvement is reported with chloroquine (1-20%) (Michelson, 1980) and phenothiazines (15%) (Alkemade, 1966). Other drugs reported to be associated with macular changes are sparsomycin (McFarlane et al, 1966), allopurinol (Pina, 1968), arsenic (Sattler, 1932) and indomethacin (Burns, 1966). The results of our study show that 19% of group II workers had macular changes, similar changes were present in 3% of control subjects.…”

Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo

“…The use of Sm was discontinued from a phase I clinical study because of a finding that, by daily doses of Sm, two out of five patients (with advanced carcinoma) developed ring scotoma after 13 days (total dose of 0.24 mg/kg) and 15 days (total dose of 0.15 mg/kg); this effect was later defined as Sm-related retinopathy [ 12 ]. Later identification by Ottenheijm et al [ 7 ] reported no observable pathological changes in the retinas of any animal treated with toxic doses of Sm and further suggested that Sm-related retinopathy was caused by a poor general condition of the patients and inappropriate drug schedules.…”

“…Sm binds primarily to the peptidyl (P) site and, because of the stabilization of the P-site/tRNA, the drug blocks the critical movement of tRNAs between the aminoacyl site and P-site, resulting in the inhibition of peptide bond formation and the inability of aminoacyl–tRNA to access the P-site [ 9 , 10 , 11 ]. Despite acute toxicity of Sm in mice [ 6 ] and Sm-related retinopathy in the phase I clinical study [ 12 ], an active testing program of the drug related to the protein biosynthesis machinery has continued [ 10 , 13 , 14 ]. Considering the effects of Sm on protein translation, the in vitro inhibitory activity of Sm against the most common and deadliest human malaria parasite, P. falciparum (3D7 and K1) [ 15 ], was evaluated.…”

Sparsomycin – a Review and Re-assessment

“…at up to 1 mg/day) against lung, cecum, and colon cancers in advanced patients was halted due to ocular toxicity (blurred vision) from the development of scotomas. 60,61 The additional biological significance of analogs of 1 became evident when it was shown that through coadministration, ethyl-deshydroxy-sparsomycin (60) at 10 mg/kg enhanced the anticancer activity of cisplatin with L1210 cells i.p. in mice 2.8-fold.…”