Melanin Affinity of a New Antituberculous Drug, Rifampicin, Investigated by Whole Body Autoradiography

Abstract

Melanin affinity has for some years been discussed in relation to the pathogenesis of drug-induced eye diseases, especially chorioretinopathy caused by phenothiazines and chloroquine (Potts 1962).While studying the distribution of rifampicin, a new, very effective antituberculous drug, I have found evidence of a possible affinity to melanin. Male mice weighing 20-25 g and female mice in late pregnancy, both of the albino NMRI strain and the brown CBA strain, were used. %-labelled rifampicin (1 mg = 7 pC) was injected i.v. The mice were sacrificed after different time intervals of from 5 min to 4 days. The whole body autoradiography technique of Ullberg (1954Ullberg ( , 1958 was used. Immediately after sacrifice the animals were deep-frozen. Sagittal sections (20-60 p thick) were cut, fixed to tape, apposed to roentgen film, and exposed for periods of up to one year. Before development, section and film were separated. The detailed results will be published elsewhere; only the difference in distribution between albino and pigmented

SELECTIVE EFFECT OF A NEW ANTITUBERCULOUS DRUG, RIFAMPICIN, ON THE c‐WAVE OF THE SHEEP ELECTRORETINOGRAM

“…rifampicin result in selective effects on pigment epithelial cell activity, as judged by the selective effects on the c-wave of the sheep ERG. I n this way, the present report may serve as a functional confirmation of the melanin affinity of rifampicin, suggested by Boman (1973) in an autoradiographic study. Furthermore, the present results point to the necessity of studies on the long-term effects of the drug, especially since standard treatment implies a daily dose of 600 mg (10 mg/kg b.w.)…”

Tissue Distribution of 14C‐Rifampicin II. Accumulation in Melanin‐containing Structures

“…review by WEHRLI & STAEHELIN 1971). One indication that RMP affects the retina is given by the study of KNAVE et al (1973), which was initiated by our findings (BOMAN 1973). KNAVE et al found a selective increase in amplitude of the c-wawe of the sheep electroretinogram (known to reflect the activity of the pigment epithelial cells) after single intravenous doses of RMP (20-40 mg/kg b.w.…”

Melanotropic Drugs and Retinal Functions

“…Recently, a new antibiotic substance, rifampicin (3-(4-methyl-l-piperazinyl-iminomethy1)-rifamycin SV), used mainly as an antituberculous agent drug, has been found to have melanin affinity (Boman 1973). Using a total body autoradiography technique, marked radioactivity was found in the uveal tracts of pigmented mice after injection of 1%-labelled rifampicin.…”