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Licit and illicit drugs
Published in Jason Payne-James, Richard Jones, Simpson's Forensic Medicine, 2019
Jason Payne-James, Richard Jones
The effects produced by salvinorin A are qualitatively different than those produced by the other hallucinogens such as LSD or mescaline, and the mechanism of action is not understood. It is known that κ-opioid receptors also play a key role in the human stress response. Because κ stimulation tends to neutralise the effects of μ1 stimulation, some feel the presence of the κ receptor may diminish the possibility of drug overdose. There is also evidence that stimulation of κ receptors in some way protects the neuron from damage; in particular, damage produced by hypoxia/ischaemia is minimised in the presence of κ receptor agonists but, again, the mechanisms involved remain totally unknown.
The Worldwide Spread of ‘Herbal Highs’
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Jessica Neicun, Darshan Singh, Eduardo Cinosi
Mitragynine and its analogues in kratom (including speciogynine (7%), paynantheine (9%), and speciociliatine (1%)) are indole alkaloids of the Corynanthe-type, possessing a monoterpene (iridoid) moiety (Takayama, 2004). Differently, 7-hydroxymitragynine, a minor constituent of M. speciosa Korth. (2%), when isolated, demonstrates a potent anti-nociceptive activity in mice (Ponglux et al., 1994), and it is considered to be a major contributory factor in the analgesic properties of M. speciosa Korth. due to its selectivity for μ- and κ- opioid receptors (Dargan & Wood, 2013). The presence of a hydroxyl group at C-7 increases the potency of 7-hydroxymitragynine to a strength of 13- and 46-fold higher than morphine and mitragynine, respectively, both in vitro and in vivo (Horie et al., 2005; Takayama, 2004; Utar, Majid, Adenan, Jamil, & Lan, 2011). This may be one of the main pharmacological markers of kratom products’ quality and potency.
CNS Receptors for Opioids
Published in Edythe D. London, Imaging Drug Action in the Brain, 2017
Richard J. Knopp, Mary Hunt, James K. Wamsley, Henry I. Yamamura
There is some evidence suggesting that [3H]EKC may show different affinities for two populations of brain κ receptors. Su (1985) measured [3H]EKC binding to guinea pig brain membranes under conditions which μ δ, and σ receptors were blocked with unlabeled ligands. These studies showed that [3H]EKC binds to high affinity (Kd = 0.7 nM, Bmax - 22 fmol/ mg protein) and low affinity (Kd = 78 nM, Bmax = 101 fmol/mg protein) sites under these conditions. However, multiple [3H]EKC binding sites to guinea pig brain membranes were not observed previously by Gillan and Kosterlitz (1982) nor subsequently by Zukin et al. (1988). Zukin et al. (1988) did observe two-site binding to rat brain membranes using [3H]EKC in the presence of μ and δ opioid receptor blockers. The high affinity site (Kd = 1.0 nM, Bmax = 16 fmol/mg protein) labeled by [3H]EKC in rat brain resembled the single κ site observed in guinea pig brain and could be selectively blocked by U-69,593, but not by U-50,488. Thus, the lower affinity site present in rat brain could be studied by measuring [3H]EKC binding in the presence of unlabeled U-69,593. The guinea pig and high affinity rat κ binding site (“κ1”) has a different pharmacological binding selectivity and brain distribution from that seen for the low affinity rat (“κ2”) binding site, suggesting that the two sites represent distinct κ opioid receptor subtypes.
What ketamine can teach us about the opioid system in depression?
Published in Expert Opinion on Drug Discovery, 2020
Laura Perez-Caballero, Victor Perez, Esther Berrocoso
Additionally, preclinical assays demonstrated that MOR and δ-opioid receptor activation and/or κ-opioid receptor blockade produces antidepressant-like effects in animal models of depression [24]. Accordingly, evidence has accumulated that severe and recurrent depression can be alleviated by multimodal opioid-based compounds [25]. However, the risk of abuse and dependence on these drugs has discouraged their use to treat depressed patients. Currently, buprenorphine offers the greatest promise as a drug to treat MDD. Buprenorphine is a partial MOR agonist and κ-opioid receptor antagonist, and it is an opioid medication commonly prescribed to treat opioid use disorder. However, it has also been seen to significantly dampen the symptoms of depression and suicidal ideation, either in monotherapy or as an add-on therapy [26]. Furthermore, recent clinical trials have shown that ALKS-5461, a combination of buprenorphine and samidorphan (a MOR antagonist), can significantly alleviate depressive symptoms, with no signs of tolerance during the treatment or withdrawal symptoms following discontinuation [27]. However, such therapy has failed to be approved by the FDA as an adjunctive treatment for MDD as additional clinical data is still required to confirm its efficacy.
The pharmacological management of dental pain
Published in Expert Opinion on Pharmacotherapy, 2020
Joseph V. Pergolizzi, Peter Magnusson, Jo Ann LeQuang, Christopher Gharibo, Giustino Varrassi
Opioid analgesics are a broad class of effective pain relievers with well-described side effects and risks for tolerance and opioid use disorder with prolonged exposure. Opioids act at the μ-, δ-, or Κ-opioid receptors located on neuronal cells in the body. Their presynaptic action inhibits the release of neurotransmitters, conferring on them powerful analgesic as well as possible psychoactive effects. Opioids also have a postsynaptic effect which can further inhibit pain signals. Thus, opioid analgesia works at multiple levels by inhibiting the release of neurotransmitters from their primary afferent terminals in the spinal cord and activating the descending inhibitory controls located in the midbrain. Opioid receptors are coupled to guanine nucleotide-binding proteins (G-proteins), the functions of which are being elucidated. Opioids act in both central and peripheral nervous systems [23]. They are effective in treating inflammatory pain but offer less benefit in neuropathic types of pain [24].
Salivary opiorphin levels in anorexia nervosa: A case–control study
Published in The World Journal of Biological Psychiatry, 2020
Elzbieta Paszynska, Monika Dmitrzak-Weglarz, Magdalena Roszak, Yves Boucher, Agata Dutkiewicz, Marta Tyszkiewicz-Nwafor, Maria Gawriolek, Justyna Otulakowska-Skrzynska, Szymon Rzatowski, Agnieszka Slopien
In the present study, opiorphin levels were not significantly different for AN patients and controls subjects, but a positive correlation was found between duration of the disease and opiorphin levels in AN patients. This is important regarding opiorphin’s influence to opioid level. The role of opioids in pain has been studied extensively, but their function in mood has received less attention (Lutz and Kieffer 2013). Evidence from animal studies reveal that µ, δ and κ opioid receptors exert distinct controls over mood-related processes although the risk–benefit ratio of agonist and antagonists as antidepressant remain difficult to evaluate (Lutz and Kieffer 2013). However, recent clinical and animal studies strengthen the observation that endogenous opioids contribute to mood disorders and appetite (Morley and Levine 1982; Yim and Lowy 1984; Lutz and Kieffer 2013), leading to the hypothesis that a chronic reduction of the supply of nutrients may increase the activity of opioids in the brain, making it easier for patients with AN to continue a restrictive diet; their restrictive diet would made them feel better, while the consumption of food would cause a worsening of mood and anxiety. In support of this hypothesis, endogenous opioids play an important role in the central regulation of appetite at the hypothalamic level (Morley and Levine 1982).