ß2 adrenergic receptor

5-HT2A serotonergic receptor

Sulphonylurea receptor (SUR1)

HER2 receptor

Thymidylate synthase and dihydrofolate reductase

Cardiac ion channels (HERG, KvLQTI, hKCNE2)

Cholesteryl ester transport protein (CETP), lipoprotein lipase (LDL), ^-fibrinogen

Apolipoprotein E4


Low tissue expression

9 Receptor downregulation


Altered ß-cell ATP-dependent potassium channel activity

Overexpression in some breast and other cancers

Overexpression in some tumor cells

Delayed cardiac repolarization

Adriamycin Paclitaxel

Other anti-neoplastics Digoxin





Protease inhibitors (most)

Albuterol Ventolin

Clozapine Tolbutamide


5-Fluorouracil Methotrexate








Tacrine Simvastatin

Resistance to treatment

Possibly 9 plasma drug concentration, risk of toxicity

Y Response, poor control of asthma

Variable drug efficacy

Y Insulin response

Receptor overexpression associated with 9 drug efficacy

Overexpression linked to development of resistance to drug anti-metabolites in tumor cells

Long Q-T syndrome, arrhythmias, torsade de pointes

Polymorphisms associated with atherosclerosis progression and response to pravastatin

Presence of allele predicts poor response to tacrine, reduced cardiovascular mortality with simvastatin aCompi[ed from Ingleman-Sundberg et al. (1999), Meyer (2000), Evans and Relling (1999), Sadee (2000) and Manicelli et al. (2000) and references therein.

concentration after a single oral dose of the drug. Other substrates of Pgp include important drugs with narrow therapeutic indices, such as chemother-apeutic agents, cyclosporin A, verapamil, terfena-dine, fexofenadine and most HIV-1 protease inhibitors (Meyer, 2000). In addition, overexpression of MDR-1 in cancer tumors has been associated with resistance to adriamycin, paclitaxel and other anti-neoplastic agents, and additional similar extrusion pumps are reported to contribute to drug resistance in various tumors (Sadee, 2000).

Another potentially important gene family with a number of reported variants that may affect function is that of the biogenic amine transporters, which play a role in the regulation of neurotrans-mitter concentrations (including serotonin, dopa-mine and GABA) in synaptic transmission (Jonsson et al., 1998). These transporters are the direct target receptors for many drugs such as anti-depressants and cocaine; polymorphisms of the serotonin transporter, in particular, have been associated with the modulation of complex behavior (Heils et al., 1996) and may play a role in treatment with specific serotonin transporter inhibitors.

Mutations in other transporter-like proteins such as the sulfonylurea receptor (SUR) that regulates ATP-sensitive K + channels and insulin secretion and the Na+/H + exchanger (NHE1) that serves as one of the target receptors for amiloride (an anti-hypertensive diuretic) are being studied and may have clinical significance in modulating the activity of many medicines (Sadee, 2000).

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