Evaluation of the lipophilic properties of opioids, amphetamine-like drugs, and metabolites through electrochemical studies at the interface between two immiscible solutions
Section snippets
Chemicals
Morphine, codeine, and amphetamine were obtained from Uquipa and Sigma (Lisbon, Portugal) as their hydrochloride salts and were used without further purification. Dihydrocodeine bitartrate was kindly provided by Knoll Lusitana (Prior Velho, Portugal).
Acetylcodeine, heroin, 6-monoacetylmorphine (6-MAM), methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), α-methyldopamine (α-MeDA) and 3-methoxy-α-methyldopamine (3-OMe-α-MeDA) were
Results and discussion
Drug metabolism is largely the biological process responsible for degradation of lipophilic drugs. The most relevant mechanism is their enzymatic conversion to more polar products, which have the propensity to be excreted relatively more rapidly. In general, the enzymes catalyze the biotransformation of the drugs by the following general reactions: oxidation, reduction, hydrolysis, deamination (phase I reactions), and conjugation (sulfation, glucuronation, methylation, acetylation—phase II
Conclusions
Lipophilicity and hydrogen-bonding ability are considered to be the most important physicochemical properties that rule the transmembrane movement of the drugs, whether used therapeutically or not [1], [5]. These parameters are also related to the affinity of the solute for the hydrophobic bilayer and its ability to leave the favorable hydrogen-bonding environment of the aqueous phase. Although initially it was thought that only neutral compounds were able to diffuse through biological
Acknowledgments
This work was supported by Portuguese Fundação para a Ciência e a Tecnologia (FCT) (projects POCTI/QUI/4XXX/2001, POCTI/QUI/41074/2001, and POCI/SAU-FCF/58330/2004). Rubin Gulaboski acknowledges the FCT of Portugal for the postdoctoral fellowship grant SFRH/BPD/14894/2004.
References (39)
- et al.
Electrochemistry at liquid/liquid interfaces: methodology and potential applications
Electrochim. Acta
(2000) - et al.
Partition and distribution coefficients of solutes and drugs in brush-border membrane-vesicles
Biochem. Pharmacol.
(1993) - et al.
The toxicity of n-methyl-α-methyldopamine to freshly isolated rat hepatocytes is prevented by ascorbic acid and N-acetylcysteine
Toxicology
(2004) - et al.
Role of metabolites in MDA (ecstasy) induced nephrotoxicity: An in vitro study using rat and human renal proximal tubular cells
Arch. Toxicol.
(2002) Liquid Interfaces in Chemical, Biological, and Pharmaceutical Applications
(2001)- et al.
Electrochemistry of Immobilized Particles and Droplets
(2005) - et al.
Electrochemistry of liquid–liquid interfaces
- et al.
- et al.
Pharmacokinetic Optimization in Drug Research
(2001) Physicochemical descriptors in property-based drug design
Med. Chem.
(2004)