Metals in Medicine: Inorganic Medicinal Chemistry - Drug Design and Discovery - page 153

Beneicial
+
(B)
Concentration
(A)
-
Harmful
FIGURE 10.1 Dose/effect diagram. Response to (A) nonessential or toxic and (B) essential elements. Note
that at sufi ciently small concentrations, toxic compounds are tolerated, while essential elements become toxic
at elevated concentrations.
with utmost care. This underlines the major point: “Specii c biological activity of inorganic com-
pounds can be achieved by proper design.”
10.2 CLASSIFICATION OF INORGANIC PHARMACEUTICALS
Inorganic drugs may be divided into three different categories (Table 10.2):
1. Active complexes . Here, the entire complex, metal ion, and ligands, determines the action.
Many coordination compounds act as neurotoxins by blocking acetylcholine receptors.
Cisplatin and other uncharged Pt(II) and Ru(II) complexes are active as antitumor drugs
(Section 10.6.4) and Bi(III) complexes are used in the treatment of gastrointestinal dis-
eases (Section 10.6.7). Insoluble salts of certain heavy metals can be applied as x-ray
contrast compounds, such as BaSO 4 . The rare earth gadolinium is used in NMR diag-
nostics. Tin coordinated to protophorphyrin inhibits heme oxygenase degradation of a
certain iron-heme product to bilirubin. The latter compound is the most frequent cause of
neonatal jaundice.
2. Active elements . Here, the metal ion is decisive for the action of the drug while the anion
or ligand only serves to keep the metal ion in solution or simply as a counter ion. The effect
of lithium in the manic-depressive psychosis is well known although not fully understood.
Interestingly, the lithium ion is counteracting both phases of the cyclic course of this
disease (Section 10.6.1). The cariostatic effect of l uoride is well established although the
mechanism is still unclear. Silver(I) and mercury(II) are potential antibacterial agents,
and silver sulfadiazine is used clinically (Section 10.6.5). Technetium (the 99m Tc isotope) is
applied in radiodiagnostics, administered as a Tc VII (CNR) + complex. The signii cance of
gold in treating rheumatoid arthritis and of antimony in treatment of “leishmaniasis” will
be discussed further in Section 10.6.
3. Active ligands . Many ligands can be delivered to or from a metal ion in the organism. The
classic iron coordination compound, nitroprusside [Fe(CN) 5 NO] 2− , releases NO, which
functions as an hypotensive agent causing smooth muscle relaxation. Some selected
chelates are presented in Section 10.5.