Opioid potency

Poulain )i Opioid Potency, cellular, physicochem Pharmacophore-based design [56]... 

Conversion from parenteral morphine or other opioids (parenteral or oral) to CR/ER/SR doseforms- Exercise particular care in the conversion process. Because of uncertainty about, and intersubject variation in, relative estimates of opioid potency and cross-tolerance, initial dosing regimens should be conservative that is, an underestimation of the 24-hour oral morphine requirement is preferred to an overestimate. To this end, estimate initial individual doses conservatively. In patients whose daily morphine requirements are expected to be 120 mg/day or less, the 30 mg tablet strength is recommended for the initial titration period. Once a stable dose regimen is reached, the patient can be converted to the 60 or 100 mg tablet strength, or appropriate combination of tablet strengths, if desired. Conversion from CR/ER/SR oral morphine to parenteral opioids - It is best to assume that the parenteral-to-oral potency is high. For example, to estimate the required 24-hour dose of morphine for IM use, one could employ a conversion of 1 mg morphine IM for every 6 mg of morphine... 

In general, a 14-OH group tended to enhance opioid potencies, par-... 

McQuay HJ, Sullivan AF, Smallman K, Dickenson AH (1989) hitra-thecal opioids, potency and lipophilicity. Pain 36 111—115. 

T. D. Egan, K. T. Muir, D. J. Hermann, D. R. Stanski, and S. L. Shafer, The electroencephalogram and clinical measures of opioid potency defining the EEG-clinical potency relationship ( fingerprint ) with application to remifentanil. Int J Pharm Med 15 1-9 (2001). 

The second application of the CFTI protocol is the evaluation of the free energy differences between four states of the linear form of the opioid peptide DPDPE in solution. Our primary result is the determination of the free energy differences between the representative stable structures j3c and Pe and the cyclic-like conformer Cyc of linear DPDPE in aqueous solution. These free energy differences, 4.0 kcal/mol between pc and Cyc, and 6.3 kcal/mol between pE and Cyc, reflect the cost of pre-organizing the linear peptide into a conformation conducive for disulfide bond formation. Such a conformational change is a pre-requisite for the chemical reaction of S-S bond formation to proceed. The predicted low population of the cyclic-like structure, which is presumably the biologically active conformer, agrees qualitatively with observed lower potency and different receptor specificity of the linear form relative to the cyclic peptide. 

Substitution of Trp by D-Trp increased the potency of somatostatin (101). Most other substitutions, however, are deleterious to biological activity. Cychc octapeptide analogues of somatostatin retain high potency one of them, CTOP, is a potent mu-opioid antagonist. 

At present, no diugs exist that can selectively activate a2-receptor subtypes. Clonidine stimulates all three a2-subtypes with similar potency. Clonidine lowers blood pressure in patients with hypertension and it decreases sympathetic overactivity during opioid withdrawal. In intensive and postoperative care, clonidine is a potent sedative and analgesic and can prevent postoperative shivering. Clonidine and its derivative brimonidine lower... 

Influencing the efficacy or potency of chemicals is a strategy used by the pharmaceutical industry as part of the drug discovery process that can be incorporated into designing safer industrial chemicals. Efficacy is the maximal effect, either therapeutic or toxic, that a chemical can achieve. Potency is a measure of the amount of a substance that is needed to attain a given response level. Opioid analgesics are examples of where structural modifications have been used to establish a relationship between structure and activity. ... 

Severe 7-1 0/1 0 Switch to a high-potency opioid regular scheduled dosing Morphine 10 mg every 4 hours Hydromorphone 4 mg every 4 hours ... 

Table 2 Antagonist Potencies and Opioid Receptor Affinities of TIPP Analogues... 

In 1995 the dipeptide H-Dmt-Tic-OH was reported to be a 6-opioid antagonist with unprecedented 6-receptor affinity (K = 0.022 nM) and 6 receptor selectivity (Kf/Kf = 150,000) [47]. However, in a direct comparison under identical assay conditions, this compound showed about 30 times lower 6-antagonist potency and 6 times lower 6-receptor selectivity... 

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