Analgesic effects of morphine and morphine‐6‐glucuronide in a transcutaneous electrical pain model in healthy volunteers

Abstract

Morphine-6-glucuronide clearly produced analgesic effects in healthy volunteers. However, the high amounts of systemic morphine-6-glucuronide needed to produce the same effects as morphine suggest that morphine-6-glucuronide barely contributes to the central nervous opioid effects after administration of analgesic doses of morphine.

Modulation of Ca2+ Channels by Heterologously Expressed Wild-Type and Mutant Human μ-Opioid Receptors (hMORs) Containing the A118G Single-Nucleotide Polymorphism

“…On the other hand, in a group of healthy volunteers, it was shown that the amount of morphine required to achieve pupil-constricting effects was not different between carriers of either allele (Lötsch et al 2002a). In another report, however, a 2.1 and 3.6 rightward shift of morphine potency was observed in heterozygous and homozygous carriers of the mutant allele, respectively (Skarke et al 2003). A study of cancer pain patients reported that a higher dose of morphine was necessary for pain relief of those homozygous for the 118G allele (Klepstad et al 2004).…”

“…Nevertheless, a volunteer-based study found that carriers of the mutant allele showed a decreased potency with respect to M-6-G-induced pupil constriction when compared with homozygous wild-type carriers (Lötsch et al 2002a). Nonetheless, another study found that 118G-carrying healthy volunteers reported less nausea and vomited less frequently when M-6-G was used as the opioid agonist (Skarke et al 2003). Moreover, in a study of two patients with renal failure, it was observed that the patient carrying the G118 allele was able to better tolerate increased plasma levels of M-6-G than the homozygous wild-type patient (Lötsch et al 2002b).…”

“…The A118G polymorphism occurs with an allelic frequency ranging from 10 to 40% (Kim et al 2004;Lötsch and Geisslinger 2005;Szeto et al 2001; dependent on population studied). Several earlier clinical studies showed that the presence of A118G polymorphism is associated with opiate effectiveness observed in patients (Janicki et al 2006;Klepstad et al 2004;Lötsch and Geisslinger 2005;Romberg et al 2004Romberg et al , 2005Shi et al 2002;Skarke et al 2003) as well as susceptibility to drug addiction (Bond et al 1998;Szeto et al 2001). On the other hand, some studies also reported a lack of a correlation between the presence of the A118G SNP and drug addiction (Arias et al 2006;Franke et al 2001;Gelernter et al 1999).…”

The mu opioid receptor A118G gene polymorphism moderates effects of trait anger-out on acute pain sensitivity

“…The variant G allele has been associated with lower acute pain responsiveness [20,32], greater beta-endorphin receptor binding [5], and greater Ca 2+ inhibition on opioid receptor activation [33]. Other work indicates the variant G allele does not influence exogenous opioid receptor binding [5], but is associated with reduced receptor expression [28,44] and increased exogenous opioid analgesic requirements [16,27,30,37,39]. Results of a preliminary study supported possible genetic moderation of the pain-related effects of anger-out by the A118G SNP [11].…”

Genotypic screening of the main opiate‐related polymorphisms in a cohort of 139 sickle cell disease patients

“…For the ABCB1 gene, we genotyped three SNPs associated with a variation (decrease or increase) of the efflux activity for many drugs: rs1128503 (C1236T) on exon 12, rs2032582 (G2677T) on exon 21 and rs1045642 (C3435T) on exon 26 [15]. Interestingly, the mutant T nucleotide for rs1045642 has been associated with a better morphine pain relief in two independent studies [16,17]. By taking these three SNPs together, some authors have defined the three main ABCB1 haplotypes [6,7]: (i) the *1 allele (C/G/C) which is the wild-type allele, (ii) the *2 allele (T/T/T), and (iii) the *2Kr allele (C/G/T).…”