Tolerance morphine

An interesting set of central nervous system properties has also been discovered and studied (Table VI-10). The work devoted to piscaine must be emphasized besides finding hypnotic properties of 2-amino-4-phenyl-thiazole on fish, the authors studied the structure of the metabolite, as well as the localization of the (radio labeled) metabolic product in various organs. Recently, thiazol-4-yl methoxyamine was shown to inhibit the development of morphine tolerance (1607). 5-Aminothiazole derivatives such as 419a were proposed as cardiovascular agents (1608, 1610). Substitution of the 5-aminothiazole radical on the cephalophosphorin structure gives a series of antibacterial products (1609). 

The CCK system shares one property with the opioid system, ie, the existence of selective nonpeptide antagonists. These include aspedicine, a natural benzodiazepine (136), and Devazepide (L-364,718 MK-329) (137). Selective, potent peptide antagonists for CCK, eg, Cl-988 and PD 134308, have been developed that maybe useful as anxiolytics and as dmgs which increase the analgesic effect of morphine but at the same time prevent morphine tolerance (138) (see Hypnotics, sedatives, anticonvulsants, and anxiolytics). 

Bohn LM, Gainetdinov RR, Lin FT et al (2000) p-Opioid receptor desensitization by (3-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720-723... 

Bleich A, Gelkopf M, Weizman T, et al Benzodiazepine abuse in a methadone maintenance treatment clinic in Israel characteristics and a pharmacotherapeutic approach. Isr J Psychiatry Relat Sci 39 104-112, 2002 Bohn LM, Gainetdinov RR, Lin FT, et al Mu-opioid receptor desensitization by beta-arrestin-2 determines morphine tolerance but not dependence. Nature 408 720— 723, 2000... 

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

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. 

Zhu Y, King MA, Schuller AGP, Nitsche JF, Reidl M, Elde RP, Unterwald E, Pasternak GW, Pintar JE. Retention of supraspinal delta-like analgesia and loss of morphine tolerance in opioid receptor knockout mice. Neuron 1999 24 243-252. 

Gudehithlu, K.R and Bhargava, H.N., Modification of characteristics of dopamine transporter in brain regions and spinal cord of morphine tolerant and abstinent rats, Neuropharmacology, 35, 169, 1996. 

Bohn L, Gainetdinov R et al. Mu-opioid receptor desensitization by beta-arestin-2 determine morphine tolerance but not dependence. Nature 2000 408 720-723. 

Opioids also interact with excitatory amino acid neurotransmitters. At lower micromolar concentrations, p agonists (e.g., DAMGO) enhance NMDA activity in the nucleus accumbens, but inhibit non-NMDA activity (Martin et al. 1997). At higher concentrations (5 pM), NMDA currents are reduced. Conversely, central administration of glutamate can precipitate a withdrawal syndrome in morphine-dependent animals, similar to the opioid antagonist naloxone. NMDA mechanisms also appear to be involved in the development of morphine tolerance. Competitive and noncompetitive NMDA antagonists and inhibitors of nitric oxide synthase reduce or eliminate tolerance to morphine (Elliott et al. 1995 Bilsky et al. 1996). However, this does not occur for tolerance to k opioids. Pharmacokinetics... 

Sunder Sharma S, Bhargava HN. (1998). Enhancement of morphine antinociception by ibogaine and noribogaine in morphine-tolerant mice. Pharmacology. 57(5) 229-32. 

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. 

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-... 

Belozertseva IV, Danysz W, Bespalov AY (2000a) Effects of short-acting NMDA receptor antagonist MRZ 2/576 on morphine tolerance development in mice. Naunyn Schmiede-bergs Arch Pharmacol 361 573-577... 

Liaw WI et al Distinct expression of synaptic NR2A and NR2B in the central nervous system and impaired morphine tolerance and physical dependence in mice deficient in postsynaptic density-93 protein. Mol Pain 2008 4 45. [PMID 18851757]... 

Mitchell JM, Basbaum AI, Fields HL A locus and mechanism of action for associative morphine tolerance. Nat Neurosci 2000 3 47. [PMID 10607394]... 

Contreras, E., Tamayo, L., Amigo, M. Calcium channel antagonists increase morphine-induced analgesia and antagonize morphine tolerance, Eur. J. Pharmacol. 1988, 148, 463-466. 

Ramkumar, V. and El-Fakahany, E.E. Increase in pH] Nitrendipine binding sites in the brain in morphine-tolerant mice, Eur. J. Pharmacol. 1984, 102, 371-372. 

Bhargava H. N. Enhancement of morphine actions in morphine-naive and morphine-tolerant mice by LY 235959, a competitive antagonist of the NMDA receptor, Gen. Pharmacol. 1997, 28, 61-64. 

Davis, A. M. and Inturrisi, C. E. D-Methadone blocks morphine tolerance and N-methyl-D-aspartate-induced hyperalgesia, J. Pharmacol. Exp. Ther. 1999, 289, 1048-1053. 

Houghton, A. K., Parsons, C. G., Headley, P. M. Mrz2/576, a fast kinetic NMDA channel blocker, reduces the development of morphine tolerance in awake rats, Pain 2001, 91, 201-207. 

Lutfy, K., Shen, K.-Z., Woodward, R. M., Weber, E. Inhibition of morphine tolerance by NMDA receptor antagonists in the formalin test, Brain Res. 1996, 731, 171-181. 

Mao, J., Price, D. D., Mayer, D. J. Thermal hyperalgesia in association with the development of morphine tolerance in rats roles of excitatory amino acid receptors and protein kinase C, J. Neurosci. 1994, 14, 2301-2312. 

Marek, P., Ben-Eliyahu, S., Vaccarino, A. L., Liebeskind, J. C. Delayed application of MK-801 attenuates development of morphine tolerance in rats, Brain Res. 1991, 558, 163-165. 

The development of acute tolerance and dependence evoked in mice by morphine can be suppressed by pretreatment with NTI. Multiple administration of either NTI or 5 NTII before and during chronic implantation with morphine pellets also substantially inhibits the development of morphine tolerance and dependence. These results suggest the use of 8 antagonists to be useful for the prevention of opioid tolerance and physical dependence without compromising the antinociceptive potency of p opioid receptor agonists (Abdelhamid et al., 1991). 

Metopon (methyldihydromorphinone) manifests the properties of tolerance and liability to addiction, but it is about twice as effective as an analgesic, and its duration of action is equal to that of morphine. Tolerance to metopon and physical dependence on the drug develop more slowly than in the case of morphine. In therapeutic doses, it produces little or no respiratory depression and still less mental dullness. Metopon thus possesses many advantages over morphine but is no longer available commercially. 

Montel H, Starke K, Taube HD (1975) Morphine tolerance and dependence in noradrenaline neurons of the rat cerebral cortex. Naunyn-Schmiedeberg s Arch Pharmacol 258 415-26 Potkin SG, Saha AR, Kujawa MJ, Carson WH, Ali M, Stock E, Strinfellow J, Ingenito G, Marder SR (2003) Aripiprazole, an antipsychotic with a novel mechanism of action and risperidone vs. placebo in patients with schizophrenia and psychoaffective disorder. Arch Gen Psychiat 60 681-90... 

Schmauss, C., and Herz, A. (1987). Intrathecally administered dynorphin-(l—17) modulates morphine-induced antinociception differently in morphine-naive and morphine-tolerant rats. Ewr. J. Pharmacol. 135, 429—431. 

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