Cross-tolerance

Anxiolytics and sedatives Excitation of the GABA receptor produces an influx of negatively charged chloride ions, which hyperpolarizes the neuron and makes it less likely to give rise to an action potential. In addition to gamma-Aminobutyric acid (GABA) itself, the GABAA receptor can also bind barbiturates and benzodiazepines. Benzodiazepine binding increases the binding of GABA and barbiturates maximize the time the pore is open. Both of these mechanisms allow for influx of chloride ions. When these drugs are taken together, especially with ethanol (drinking alcohol), there is a disproportionate increase in toxicity because the effects of both occur simultaneously and add up since they act on the same receptor at different sites. Convergence upon the GABAA receptor is why tolerance for one drug in the group will most likely cause cross-tolerance for the other drugs in the group. Stimulants Cocaine, amphetamines, methylphenidate and ephedrine block the reuptake of dopamine and norepinephrine. With increasing doses, amphetamines also cause the direct release of these neurotransmitters. Psychedelics Serotonergic psychedelics act through modulation of serotonin receptors. Most of these drugs share a high affinity for the 5-HT2A receptor subtype, known to result in their common perceptual and psychological effects. ==Cross-tolerance between drugs of different classifications==

Sometimes cross-tolerance occurs between two drugs that do not share mechanisms of action or classification. For example, in rats some amphetamine-like stimulants have been shown to exhibit cross-tolerance with caffeine, though this effect was not observed with amphetamine itself. It is likely that this mechanism of cross-tolerance involves the dopamine receptor D1. Amphetamines also have cross-tolerance with pseudoephedrine, as pseudoephedrine can block dopamine uptake in the same manner that amphetamines do, but less potently. Alcohol is another substance that often exhibits cross-tolerance with other drugs. Findings of cross-tolerance with nicotine in animal models suggest that it is also possible in humans, and may explain why the two drugs are often used together. Numerous studies have also suggested the possibility of cross-tolerance between alcohol and cannabis. Cigarette smoking produces increased metabolic tolerance to caffeine due to upregulation of the CYP1A enzyme family (see aryl hydrocarbon receptor). ==References==