Dependence and tolerance

In conclusion, it is thought that the best agonists bind swiftly to the receptor, pass on their message and then leave quickly. Antagonists, in contrast, tend to be slow to add and slow to leave. 

It has been discovered that starving a target cell of a certain neurotransmitter induces that cell to synthesize more receptors. By doing so, the cell gains a greater sensitivity 

It is only in recent years that medicinal chemists have begun to understand receptors and drug receptor interactions. This increased understanding should revolutionize the subject in the years to come. 

Receptor desensitization, internalization, and/or down-regulation may play a role in the development of tolerance to opioid receptor agonists (Clark et al. 

The process by which the heating of a fermented mixture increases its alcohol content. 

Alcohol virtually always is drunk in one of the three major classes of alcoholic beverages beer, wine, and hard liquor (also called distilled spirits). For their manufacture, all these beverages depend on the process of fermentation, and hard liquor on the further process of distillation. Fermentation begins when sugar is dissolved in water 

A variety of alcoholic beverages is available to the interested consumer. 

In the United States, alcohol percentage is denoted by volume. This calculation is straightforw ard 16 ounces of a beverage that is 50% ethanol contains 8 ounces of alcohol. Another way of expressing alcohol content is by w eight, w hich is done, for example, in Britain. 

The proportion of alcohol In a beverage, by volume. Proof typically Is used In reference to distilled spirits and equals twice the percentage of alcohol. 

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AVP is excitatory in the ventral hippocampus, either directly or by potentiation of glutamatergic responses. An inhibitory effect has been observed in AVP may be involved in the formation of long-term potentiation and thus learning and memory. However, AVP is proconvulsive, may augment the formation of dmg tolerance and dependence, and affects cardiovascular regulatory processes. 

They act as analgesics by inhibiting release of nociceptive neurotransmitters from primary afferent terminals as well as by depressing post-synaptic potentials on second order neurons. Opioid receptors are also present on some nociceptors and their expression and peripheral transport is increased upon peripheral inflammation. Peripheral opioid analgesia has been established in animal models. Although clinical studies have yielded mixed results so far, this field holds great promise. Despite side effects, such as euphoria, dysphoria, sedation, respiratory depression and obstipation and tolerance and dependence phenomena which arise upon... 

Kraus J, Bomer C, Giannini E, HoUt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64 876-884 Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling implications in opioid tolerance and dependence. [Review] [123 refs]. Neuropharmacology 47(Suppl 1) 300-311... 

OF TOLERANCE AND DEPENDENCE. Charles Wm. NCADI out of stock NTIS PB 89-103279/AS 36.95... 

C. Effect of 5-Opioid Antagonists on the Development of Morphine Tolerance and Dependence... 

The three prototype mixed p agonist/S antagonists described in this chapter have excellent potential as analgesics with low propensity to produce tolerance and dependence. The pseudotetrapeptide DIPP-NH2[ ] has already been shown to produce a potent analgesic effect, less tolerance than morphine, and no physical dependence upon chronic administration. In preliminary experiments, the tetrapeptides DIPP-NH2 and DIPP-NH2[T] were shown to cross the BBB to some extent, but further structural modifications need to be performed in order to improve the BBB penetration of these compounds. The Tyr-Tic dipeptide derivatives can also be expected to penetrate into the central nervous system because they are relatively small, lipophilic molecules. In this context, it is of interest to point out that the structurally related dipeptide H-Dmt-D-Ala-NH-(CH2)3-Ph (SC-39566), a plain p-opioid agonist, produced antinociception in the rat by subcutaneous and oral administration [72], As indicated by the results of the NMR and molecular mechanics studies, the conformation of the cyclic p-casomorphin analogue H-Tyr-c[-D-Orn-2-Nal-D-Pro-Gly-] is stabilized by intramolecular hydrogen bonds. There-... 

Abdelhamid EE, Sultana M, Portoghese PS, Takemori AE. Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice. J Pharmacol Exp Ther 1991 258 299-303. 

Fundytus ME, Schiller PW, Shapiro M, Weltrowska G, Coderre TJ. The highly selective 6-opioid antagonist H-Tyr-Tic1P[CH2-NH]Phe-Phe-OH (TIPP[Tf]) attenuates morphine tolerance and dependence. Eur J Pharmacol 1995 286 105-108. 

Tolerance and dependence occur with both BZD and non-BZD compounds abrupt discontinuation results in withdrawal phenomena such as anxiety, agitation, restlessness, and hypertension. Tolerance, especially to the hypnotic effect, is known to occur, so an increase in dose is required to obtain the same effect (Liappas et al. 2003). 

Sharma S, Klee W, Nirenberg M. Dual regulation of adenylate cyclase accounts for narcotic tolerance and dependence. Proc Natl Acad Sci USA 1975 72 3092-3096. 

Upregulation of the cAMP pathway may be a common mechanism by which a number of neuronal cell types respond to chronic opiates and develop tolerance and dependence (see Ch. 56). There is also evidence that similar mechanisms involving alterations in the cAMP second-messenger and protein phosphorylation pathway may mediate aspects of addiction to other types of drugs of abuse, for example, cocaine and alcohol [66],... 

Chronic insomnia calls for careful assessment for a medical cause, non-pharmacologic treatment, and careful use of sedative-hypnotics (intermittently to prevent tolerance and dependence). 

The clinical consequences of the currently used benzodiazepines range from sedation, muscle relaxation, seizure reduction, anxiolysis, and hypnosis. Clearly, it would be highly desirable to be able to separate some of these effects. In addition, it would be useful to reduce other undesirable consequences such as development of tolerance and dependence, abuse, synergistic interaction with ethanol, and memory impairment (for a comprehensive review see [22]). Animal models for some of the aforementioned conditions, in combination with transgenic mouse technology, have recently led to a deeper understanding of the contribution some of the individual a subunits make to these behaviors. 

Tolerance and dependence are characteristic of repeated administration of opioid drugs, which limits their use in treatment. It has been proposed that tolerance results from desensitization of opioid receptors and altered... 

Ahlijanian MK, Takemori AE. (1986). The effect of chronic administration of caffeine on morphine-induced analgesia, tolerance and dependence in mice. EurJ Pharmacol. 120(1) 25-32. 

Trouvin JH, Jacqmin P, Rouch C, Lesne M, Jacquot C. (1987). Benzodiazepine receptors are involved in tabernanthine-induced tremor in vitro and in vivo evidence. EurJ Pharmacol. 140(3) 303-9. Trujillo KA, Akil H. (1991). Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science. 251(4989) 85-7. 

Abrams J. 1980. Nitrate tolerance and dependence. American Heart Journal 99 113-123. 

Drug and alcohol dependent patients Use with caution in patients with alcoholism and other drug dependencies due to the increased frequency of benzodiazepine tolerance and dependence observed in these patient populations. 

It is beheved that phenomena such as sensitization, tolerance and drug-dependence might also involve synaptic plasticity. In fact, numerous studies indicate that NMDA receptor antagonists block sensitization to amphetamine and cocaine as well as tolerance and dependence to ethanol and opioids in animal models (Trujillo and Akil 1991 Pasternak and Inturrisi 1995 Trujillo and Akil 1995 Mao 1999). Recent studies indicate that the uncompetitive NMDA receptor antagonists dextromethorphan, memantine and neramexane not only prevent the development of morphine tolerance, but also reverse estabhshed tolerance in the continuing presence of this opioid, prevent the expression of withdrawal symptoms in rats (Popik and Skolnick 1996 Popik and Danysz 1997 Popik and Kozela 1999 Houghton et al. 2001) and attenuate the expres-... 

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