Cross-tolerance, drug

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. 

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 ... 

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

At the least, we should more systematically classify those drugs that produce a psychedelic sequence in man and show cross tolerance with LSD with respect to the different receptor systems that apparently rank order these drugs in terms of their potency. Such rank order effects have been noted on molluscan ganglia (35) in the clam heart on excitation of cardiac muscle in liver fluke on glycolysis... 

Animal drug discrimination paradigms show cross-tolerance between cathinone, cathine, and amphetamine (Schechter 1990). S(-i-)methcathi-... 

The A -demethylation pathway is common to the metabolism of Ml 25 (Vllf) and morphine, both drugs being converted to secondary amines by liver micro-somes under the same condition [55]. Reaction rates were depressed when microsomes from rats repeatedly treated with Ml25 or morphine were used. In the same work, rats were-shown to become tolerant to the pharmacological effects of M125 (shock avoidance and tail clip tests) and cross tolerance to morphine was also found. 

Tolerance to many of the effects of the depressants develops. Unlike opioids, barbiturate and benzodiazepine tolerance develops slowly. Also, tolerance is incomplete in some instances or does not influence some pharmacological effects. One such exception is the lack of tolerance to barbiturate lethality. The lethal dose in a tolerant individual is not much different from that of the general population. Cross-tolerance develops to some degree between the depressant classes of drugs. 

Unlike benzodiazepines, buspirone is not associated with sedative or abuse problems, but some clinicians have observed that bus-pirone s anxiolytic properties do not appear to be as potent as those of benzodiazepines, particularly in patients who have previously received a benzodiazepine. Because buspirone is not sedating and has no psychomotor effects, it has a distinct advantage over benzodiazepines when optimal alertness and motor performance are necessary. Response to buspirone occurs in approximately 2-4 weeks. Buspirone does not show cross-tolerance with benzodiazepines and other sedative or hypnotic drugs such as alcohol, barbiturates, and chloral hydrate. Therefore, buspirone does not suppress benzodiazepine withdrawal symptoms. In anxious patients who are taking a benzodiazepine and who require a switch to buspirone, the benzodiazepine must be tapered gradually to avoid withdrawal symptoms, despite the fact that the patient is receiving buspirone. 

Cross-tolerance Tolerance to a pharmacologically similar drug one drug may be substituted for another. 

Cross tolerance is development of tolerance to pharmacologically related drugs e.g. morphine and barbiturates. 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in the need for an increase in the dose required to maintain symptomatic improvement or to promote sleep. It is important to recognize that partial cross-tolerance occurs between the sedative-hypnotics described here and also with ethanol (see Chapter 23)—a feature of some clinical importance, as explained below. The mechanisms responsible for tolerance to sedative-hypnotics are not well understood. An increase in the rate of drug metabolism (metabolic tolerance) may be partly responsible in the case of chronic administration of barbiturates, but changes in responsiveness of the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics. In the case of benzodiazepines, the development of tolerance in animals has been associated with down-regulation of brain benzodiazepine receptors. Tolerance has been reported to occur with the extended use of zolpidem. Minimal tolerance was observed with the use of zaleplon over a 5-week period and eszopiclone over a 6-month period. 

The psychomotor stimulants, cocaine and D-amphetamine, are considered together because they share a similar psychopharmacological profile.19 20 Low to moderate doses of both drugs given acutely to nontolerant, nonanxious subjects produce increases in positive mood (euphoria), energy, and alertness. Experienced cocaine users were unable to distinguish between intravenous (IV) cocaine and D-amphetamine,21 and cross-tolerance between cocaine and D-amphetamine with respect to their anorectic effect has been demonstrated.22 Additionally, the toxic psychosis observed after days or weeks of continued use of both psychostimulants is very similar. The fully developed toxic syndrome, characterized by vivid auditory and visual hallucinations, paranoid delusions, and... 

Cross-tolerance and cross-dependence The ability of one drug to suppress the... 

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