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Fentanyl and Related Opioids
Published in Ornella Corazza, Andres Roman-Urrestarazu, Handbook of Novel Psychoactive Substances, 2018
Esther Papaseit, Magí Farré, Clara Pérez-Mañá, Adriana Farré, Francina Fonseca, Marta Torrens
Fentanyl, N-(1-phenethyl-4-piperidyl) propionanilide, is a synthetic opioid, structurally related to pethidine (meperidine) which is composed of a phenylalkyl moiety, a piperidinyl ring, and a propylalkylamide moiety. Since its appearance on the market in the 1960s, fentanyl has been the most potent (strongest) opioid prescribed for anaesthesia, surgery premedication, and chronic pain management. In the mid-1990s, a novel fentanyl skin patch was released for chronic pain relief, and from then on, other new fentanyl preparations (oral transmucosal-‘lollipop’, buccal tablet, buccal soluble film, sublingual, tablet nasal, and spray) have become available for the same indication. In addition, within the last decades, different fentanyl analogues, drugs designed to mimic fentanyl pharmacological effects, have been developed for human use (sufentanil, alfentanil, remifentanil), veterinary medicine (carfentanil and thiofentanil), and for research purposes (lofentanil) (Stanley, 2014; United Nations Office on Drugs and Crime [UNODC], 2017b).
Vagal Receptor Transport
Published in Sue Ritter, Robert C. Ritter, Charles D. Barnes, Neuroanatomy and Physiology of Abdominal Vagal Afferents, 2020
In contrast to these results obtained by in vitro autoradiography, when opiate receptors were labeled in vivo with 3H lofentanil, an accumulation of binding sites was present on both sides of the ligature.15 In these studies the ligatures were placed approximately 1.5 cm below the level of the nodose ganglion and 10 μcurries of 3H lofentanil were injected intravenously into rats at different time intervals prior to sacrifice. Nerve segments above and below the ligature were removed and counted for radioactivity. The results demonstrated that there was a buildup of 3H lofentanil in the nerve on both sides of the ligature and, as demonstrated in Figure 5, the magnitude of accumulation was significantly greater distal rather than proximal to the ligature site. Four hours after the in vivo3H lofentanil injection, labeling was maximal proximal to the ligature site. A delay of 16–24 hours between 3H lofentanil injection and sacrifice was necessary to reach a maximum accumulation distal to the site. The rapid appearance in the proximal part was ascribed to the short distance between the ligature and the nodose ganglion. The long distance between the ligature and the nerve terminal located in the gut, heart and lung were thought to explain the delayed accumulation in the distal segment. In rats in which a ligature was not used there was an accumulation of 3H lofentanil in the nodose ganglion. This accumulation was maximal 16 hours following injection and gradually fell off. This accumulation was blocked by vagotomy or capsaicin treatment.
Tramadol induces changes in Δ-FosB, µ-opioid receptor, and p-CREB level in the nucleus accumbens and prefrontal cortex of male Wistar rat
Published in The American Journal of Drug and Alcohol Abuse, 2019
Mitra-Sadat Sadat-Shirazi, Nima Babhadi-Ashar, Solmaz Khalifeh, Sarah Mahboubi, Hamid Ahmadian-Moghaddam, Mohammad-Reza Zarrindast
The results of the current study revealed that the MOR levels increased in animals which were treated with tramadol. Minami et al. indicated that tramadol had a direct effect on opioid receptors, of which this affinity is modest for the MOR and lesser for δ and κ-opioid receptors (5). Moreover, Nakamura et al. indicated that tramadol causes place conditioning via MOR (23). They also demonstrated that tramadol and its active substrate M1 activated MOR in the Ventral tegmental area (VTA) and increased dopamine release in the NAC, which is the initiation of the rewarding effect of tramadol (23). It is noteworthy that opioid receptors, especially the MOR, are critical elements in developing dependence and tolerance to opioid drugs such as tramadol (24). MOR are expressed at high levels in the NAC, cortex, amygdala, and hippocampus (25). Real-time PCR data revealed that chronic morphine administration did not change the mRNA level of MOR in the NAC (26). However, in both acute and chronic treatment, our current results revealed that tramadol could elevate the level of MOR in the NAC and the PFC. After the activation of MOR, desensitization occurs which varies with the signaling pathway, depending on the agonist type (27). For instance, fentanyl, sufentanil, and lofentanil desensitize MOR by uncoupling MOR from adenylyl cyclase (28). Another research showed that morphine and remifentanil desensitized MOR via cAMP, but not mitogen-activated protein kinase (MAPK) pathway (29). With this background, we propose that desensitization of MOR by tramadol might be a reason for increasing MOR levels in these regions.