In order to understand the molecular interactions of drugs with melanin, synthetic soluble (-)-dopa-melanin was prepared in deuterium buffer. The spectra of various drug moieties with the pigment at 30 degrees C were studied employing the line width measurements obtained with a pulse NMR (AF270) instrument. As compared to drug effects in fresh melanins (48 h), the aged melanins (greater than or equal to 168 h) gave consistent spectral measurements, even in dilute solutions of pigment. NMR signals of aromatic and N-methyl protons of drugs were relatively easy to quantify and, in the presence of melanin, line broadening of various drug moieties occurred. The line widths of the N-methyl groups of acetylcholine (3.02 ppm), the N-methyl group of atropine (2.52 ppm), N-isopropyl of isoprenaline bitartrate (1.14 ppm) and N-ter-butyl of timolol maleate (1.22 ppm) in the presence of the pigment were increased. Line widths associated with acetate, bitartrate, maleate or tropic acid, however, were not altered by the melanin. This indicates the specificity of the interaction between drug moieties and the site(s) of melanin. Based on the line width measurements of N-methyl protons of ephedrine, two dissociation constants were obtained (Kd1 2.08 mM and Kd2 greater than 20 mM). The constants for atropine melanin complex were Kd1 0.79 mM and Kd2 greater than 6 mM. Furthermore, based on N-methyl resonances, it appears that atropine and ephedrine compete for at least one common interacting site of the melanin polymer.