Brain opioid receptor distribution

Distribution - Following a 1 mg parenteral dose, nalmefene was rapidly distributed. A 1 mg dose blocked more than 80% of brain opioid receptors within 5 minutes after administration. The apparent volumes of distribution centrally and at steady state are 3.9 and 8.6 L/kg, respectively. Over a concentration range of 0.1 to 2 mcg/mL, 45% is bound to plasma proteins. 

Figure 5.1 Visualization of the distribution of the DA transporter, D3 receptor, and K2-opioid receptor in the human brain of a drug-free control subject and a representative cocaine overdose victim. (A, B) The DA transporter was measured using [3H]WIN 35,428 (2 nM) as described previously. (C, D) The D3 receptor was measured using [3H]-(+)-7-OH-DPAT (1 nM) in the presence of GTP (300 m/W) to enhance the selective labeling of the D3 receptor subtype over the D2 receptor subtype as described previously. (E, F) The K2-opioid receptor subtype was measured using [125l]IOXY on tissue sections pretreated with BIT and FIT to occlude binding to the p- and 8-opioid receptors, respectively.

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DePaoli A, Hurley K, Yasuda K, Reisine T, Bell GI. Distribution of kappa opioid receptor mRNA in adult mouse brain An in situ hybridization histochemistry study. Mol Cell Neurobiol 1994 5 327-335. 

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Opioid receptors and their precursor mRNAs are distributed throughout the brain and spinal cord. High levels of opioid binding have been found in the ascending pathways for nociceptive transmission, including the... 

Methyinaltrexone is a quaternary derivative of the opioid antagonist, naltrexone. The addition of the methyl group forms a compound with greater polarity and lower lipid solubility, so that it is poorly absorbed, and does not cross the blood-brain barrier. Methyinaltrexone distributes selectively (>200-fold selectivity) to peripheral receptors. In human trials it prevented morphine-induced delay in gastrointestinal transit time, while sparing centrally mediated analgesic effects. 

Microdialysis was used to assess morphine 6-beta-D-glucuronide (M6G) and morphine brain distribution in extracellular fluid after systemic administration in rats (Stain-Texier). M6G penetrated into the brain, was distributed and trapped preferentially than morphine in the extracellular fluid and therefore was available to bind at opioid receptors, explaining how M6G induces more potent central analgesia than morphine. 

Mansour A, Thompson RC, Akil H, Watson SJ (1993) Delta opioid receptor mRNA distribution in the brain comparison to delta receptor binding and proenkephalin mRNA. J Chem Neuroanat 6 351-362. 

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