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INNOSC Theranostics and
Pharmacological Sciences Alpha-2A receptor agonist and addiction

Today’s treatment of OUDs often begins with an overdose is a logical response to an OUD crisis and opioid overdose
intervention in an emergency or hospital department, epidemic. Detoxification and abstinence are associated
followed by a rapid transition to buprenorphine. Although with more deaths, overdoses, and medical problems. It
treatment algorithms for OUD have been well described, is of interest that the combination of clonidine and long-
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they are often one-size-fits-all. Many patients not engaged acting naltrexone maybe as effective and comparable in
in this transition from active use to treatment are lost to some cases to just using buprenorphine alone, to detoxify
follow-up, drop out, or continue receiving buprenorphine patients for opioid treatment (X: BOT). However, work
or methadone for years. Some patients who want to be Lee et al. in an attempt to determine the potential
detoxify or switch to monthly naltrexone injections can effectiveness of naltrexone versus buprenorphine did not
benefit from using non-opioid medications, such as provide definitive results. As suggested by Lee et al. except
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clonidine or lofexidine, to treat withdrawal symptoms. for health and other professionals, successful outcomes
Non-opioid treatment options are essential for physicians are not generally the case. This prompts the question:
and those at risk for OUDs. Clonidine is important in What are the logical short- and longer-term outcomes
the transition of physicians from OUDs to naltrexone to be achieved for OUD patients? Typically, a positive
and the transition of thousands of patients maintained OUD outcome is defined by not dying, attending clinics
on methadone and buprenorphine to naltrexone. MAT to receive opioid maintenance medication, or avoiding
discontinuation is an important overdose risk factor, and overdoses and emergency room visits. In physicians,
clinicians often recommend naltrexone after long-term outcomes are distinctly different, focusing on returning
agonist maintenance for OUDs. Clonidine may have to full premorbid function. These include negative urine
additional roles in reducing withdrawal distress from other tests, attending Caduceus meetings, following a detailed
drug cravings during MAT maintenance and in neonates. psychosocial post-evaluation treatment plan, and
An intriguing concept is that receptor tolerance entails achieving positive social, job return-performance, and
the enhancement of receptor regulation mechanisms, such spouse-partner ratings.
as desensitization and internalization. Furthermore, as While extensive research is required, it is necessary
suggested by Christie, the adaptations leading to cellular to revisit the issues of depression, suicide, and despair
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tolerance are multifaceted, involving several significant associated with chronic iatrogenic opioid administration
processes, including upregulation of cAMP/PKA and using MATs. Treatment without a focus on recovery
cAMP response element-binding signaling, as well as and without addressing “dopamine homeostasis” may
mitogen-activated protein kinase cascades in opioid- contribute to a revolving door, where many patients with
sensitive neurons. These mechanisms have implications OUD relapse and overdose, repeatedly receiving the same
not only for tolerance and withdrawal but also for synaptic treatment without long-term success. 70,154
plasticity during cycles of intoxication and withdrawal.
Such adaptations could potentially impact the likelihood 5. Locus coeruleus therapeutics:
of relapse. Applications to other areas – behavioral
It is also important to point out that some early addictions
experiments suggested that the LC might not be a As discussed in the current article, dysfunction of the LC-NA
primary site for opioid-induced withdrawal. However, a system affects many neuropsychiatric and neurological
complete lesion of catecholaminergic nerve cell bodies in diseases, including opioid and other drug withdrawal
the LC, achieved by intracerebroventricular injection of symptomatology, Parkinson’s disease, depression, anxiety,
6-hydroxydopamine, resulted in the total abolition of SS14- post-traumatic stress disorder, ADHD, and Alzheimer’s
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specific binding in the structure. Specifically bound [ I] disease. It has become evident that even in cases where the
[Tyr ,D-Trp ]SS14 and TH+ cell density overlapped with LC is not directly involved in the disorder, manipulating
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0]
SS14. Furthermore, it is known that tyrosine hydroxylase LC activity could improve health outcomes. Disruption
is the rate-limiting enzyme involved in the synthesis of the feedback loop supporting the dysfunction could
of catecholamines, especially dopamine. Gagne et al. re-establish a healthy physiological response, moving
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revealed that somatostatin binding sites are uniformly the patient toward normal daily activity. There are
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localized on all noradrenergic neurons of the LC. There is selective NA reuptake inhibitors, such as atomoxetine,
abundant evidence supporting the role of catecholamines, used for opioid withdrawal. NA agonistic agents are
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especially in opioid-induced withdrawal and LC. 152 used for ADHD, and for Parkinson’s disease, the alpha-2
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The shift to long-term or perpetual use of powerful and adrenergic receptor antagonist lofexidine is used for
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addictive opioids such as buprenorphine and methadone cognitive dysfunction 158,159 and reboxetine for depression.
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Volume 7 Issue 3 (2024) 10 doi: 10.36922/itps.1918