Cross tolerance

Cross tolerance is a form of tolerance which may develop to the effects of pharmacologically related diugs, particularly to those acting at the same receptor. 

Pasternak GW (2001) Incomplete cross tolerance and multiple p opioid peptide receptors. Trend Pharmacol Sci 22 67-70... 

Not cross-tolerant to benzodiazepines and should not be used for acute withdrawal high doses may be used to treat anxiety disorders to help maintain long-term discontinuation after abstinence has been achieved. 

GHB treatment in mice, tolerance develops to both the hypolocomotion and cataleptic effects of the drug (Itzhak and Ali 2002). There is also preclinical evidence of cross-tolerance and cross-dependence of GHB with alcohol (Colombo et al. 1995 Fadda et al. 1989). As described in the earlier section on clinical pharmacology, GHB and its analogues have been used in humans in the treatment of alcohol withdrawal. Nicholson and Balster (2001) reviewed the evidence for cross-tolerance and cross-dependence of GHB with alcohol. 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Anandamide, in vivo, was shown to produce the four characteristic effects of cannabimimetics, namely, analgesia, hypothermia, hypoactiv-ity, and catalepsy (Smith, 1994 Fride, 1993 Crawley, 1993). These four effects are not unique to cannabimimetics when they are produced together, however, they are highly predictive of cannabimimetic activity (Martin, 1991). Anandamide was found to be less potent than delta-9-THC in producing these behavioral effects in mice (Fride, 1993). It has quicker onset and shorter duration of action, the latter because of rapid catabolism. Cross-tolerance studies, in which pretreatment of mice with delta-9-THC produced tolerance to most of the pharmacological effects of anandamide and vice versa, indicate that both drugs act on the same receptor (Jarbe, 1998). 

Cross-tolerance A condition where an individual who is tolerant to the pharmacological effects of one member of a drug family also shows tolerance to other members of that family. Cross-dependence allows drug substitution during detoxification (e.g., methadone for heroin or clomethiazole for ethanol), so reducing the severity and potential danger of withdrawal symptoms. 

There are two main treatments for the opiate withdrawal syndrome. One is replacement therapy with methadone or other X agonists that have a longer half-life than heroin or morphine, and produce mild stimulation rather than euphoria. They also produce cross-tolerance to heroin, lessening heroin s effect if patients relapse. Withdrawal is also treated with the 0C2 agonist clonidine, which inhibits LC neurons, thus counteracting autonomic effects of opiate withdrawal — such as nausea, vomiting, cramps, sweating, tachycardia and hypertension — that are due in part to loss of opiate inhibition of LC neurons. 

Shaaltiel, Y., A. Glazer, P.F. Bocion, and J. Gressel. 1988. Cross tolerance to herbicidal and environmental oxidants of plant biotypes tolerant to paraquat, sulfur dioxide, and ozone. Pestic. Biochem. Physiol. 31 13-23. 

What are the precise synaptic mechanisms that mediate tolerance and cross tolerance to LSD Are they different than the basic processes that mediate the acute actions of these drugs ... 

Freedman, D. X., and Aghajanian, G. K. (1959) Time parameters in acute tolerance, cross tolerance, and antagonism to psychotogens. Fed. Proc, 18 390 (Abstr.). 

Mg/kg LSD is given at 3 hourly intervals with the animals being tested only after the last injection (32). Cross tolerance has been observed to other indole and phenylalkylamine hallucinogens (11). Similar effects were also reported for other hallucinogens (10) with an order of potency that paralleled that seen in humans (2) that is, the (hallucinogenic) -isomer of LSD was about 10 times as potent as psilocybin and 100 times as potent as mescaline (10). 

Abramson, H. A., Rolo, A., Sklarofsky, B., and Stache, J. (1960) Production of cross-tolerance to psychosis-producing doses of lysergic acid diethylamide and psilocybin. J. Psychol., 49 151-154. 

Appel, J. B., and Freedman, D. X. (1968) Tolerance and cross-tolerance among psychotomimetic drugs. Psychopharmacologia, 13 267-274. 

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