The Melanin Affinity of Chloroquine and Chlorpromazine Studied by Whole Body Autoradiography

Lindquist, Nils Gunnar; Ullberg, Sven

doi:10.1111/j.1600-0773.1972.tb03310.x

Cited by 93 publications

(16 citation statements)

References 52 publications

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“…Similar distribution patterns for chlorpromazine and chloroquine have recently been reported by Lindquist & Ullberg (1972) using the same technique. The frequency of ocular side-effects during treatment with these drugs has been related to the total dose and the duration of therapy.…”

Section: Figsupporting

confidence: 85%

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

Boman

1973

Acta Ophthalmologica

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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

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Section: Figsupporting

confidence: 85%

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

Boman

1973

Acta Ophthalmologica

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“…The pattern of I4C-thiouracil uptake in melanin differed essentially from that of other drugs with a high accumulation in melanin, like phenothiazines and chloroquine ( fig. 2b) (Lindquist & Ullberg 1972). Thus, the foetal eye showed a high accumulation while it was lower in the maternal eye.…”

Section: Resultsmentioning

confidence: 93%

“…t h e eye of foetuses a n d young animals b u t n o t in o l d animals. Unlike m a n y other drugs, mainly polycyclic amines which accumulate in preformed (adult) melanin (Potts 1964;Lindquist & Ullberg 1972), thiouracil is n o t b o u n d t o isolated beef eye melanin in vitro.…”

mentioning

confidence: 99%

Incorporation of Thiouracil and some Related Compounds into Growing Melanin

Dencker

Larsson

Olander

et al. 1981

Acta Pharmacologica et Toxicologica

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Several drugs, mainly polycyclic amines, are accumulated in melanin‐containing tissues. They are bound to preformed melanin (both in vivo and in vitro). Thiouracil is accumulated into melanin according to another principle: It is incorporated as a false precursor during melanin formation. It is thus taken up only in growing melanin, e.g. in the eye of pigmented mouse foetuses or in melanomas. The acceptance of a foreign substance during the formation of a foetal tissue seems theoretically important. We are also interested in the practical viewpoint of using false melanin precursors as selective melanoma seekers. Some related substances are therefore compared with respect to incorporation into growing melanin. The thiouracil uptake in the ocular melanin of a 5 day old mouse was 276 times higher than that of a 3 month old mouse based on weight units of melanin. Thiourea is incorporated in growing melanin as well but also binds slightly to preformed melanin. Uracil and fluorouracil showed no specific uptake into growing melanin. It thus seems as if the sulfur is essential for the incorporation into the melanin polymer. 35S‐thiouracil and 2‐thio(2‐14C)uracil showed the same high uptake, indicating that at least part of the uracil moiety is incorporated together with the sulfur. There seems to be a relation between the property to be incorporated into melanin and the thyrostatic activity. Both in the formation of melanin and thyroid hormones, tyrosine is the physiological precursor and both reactions are catalyzed by oxidizing enzymes. Properly labelled thiouracil derivatives seem to be promising melanoma seekers for diagnostic and radiotherapeutic purposes.

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“…After the whole body autoradiography with labelled chloroquine radioactivity was detected in the uveal tract of pigmented mice one year after a single i.v. dose (Lindquist and Ullberg 1972). In our study, the persistence of isoxsuprine in melanin for longer periods than 24 h is now known, since the mice killed after 4, 14 and 28 days were all albino mice.…”

Section: Discussionmentioning

confidence: 56%

Melanin affinity: a possible explanation of isoxsuprine retention in the horse

Törneke

Larsson

Appelgren

2000

Equine Veterinary Journal

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Summary Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H‐isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The Kd values were 0.02 mmol/l and 1 mmol/l, and the Bmax values were 0.2 μmol/mg and 2 μmol/mg, respectively. A low affinity site with approximately the same Kd and Bmax as keratin was also detected for melanin. 3H‐isoxsuprine was found to have affinity to pigmented horse skin after incubation in vitro and microautoradiography. We believe that affinity to melanin and possibly also to keratin can cause retention of the drug in the body and therefore explain the prolonged excretion of low levels of isoxsuprine in the horse.

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The Melanin Affinity of Chloroquine and Chlorpromazine Studied by Whole Body Autoradiography

Cited by 93 publications

References 52 publications

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

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

Incorporation of Thiouracil and some Related Compounds into Growing Melanin

Melanin affinity: a possible explanation of isoxsuprine retention in the horse

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