Further experimentation revealed a form of molecular interaction between the adenosine-2A receptors and dopamine receptors. These receptors reportedly form heterodimers with active participation in the physiological process. The resulting A2A– D2 heterodimers also reportedly have a signal transduction mechanism (GαQ/Z protein-mediated) that is different from A2A (GαS protein-mediated) or D2 (GαI/O protein-mediated) receptors. The interactions between the purinergic receptors and the dopamine receptors are complex on multiple levels. In experimental models, some antagonists of adenosine- 2A receptors reportedly inhibited the firing activity of norepinephrine neurons of the LC and dopamine neurons of the ventral tegmental area (VTA), and some antagonists of adenosine-2A receptors also reportedly reverse the inhibition of norepinephrine and dopamine neurons. Interactions of this nature further promot the hypothesis that antipsychotics exert therapeutic effects partially by leveraging the actions of multiple purinergic receptors in the central nervous system. Potentiation effects have also been described in this regard, with different adenosine-2A receptor antagonists impacting the extracellular levels of catecholamines. For instance, an adenosine-receptor antagonist ZM 241385 reportedly potentiates the effect of haloperidol on nucleus accumbens (NAcc) dopamine and prefrontal cortex (PFC) norepinephrine. Since adenosine-2A receptors have shown impressive results in modulating central catecholamine transmission, researchers have repeatedly studied adenosine-2A receptor ligands as potential drugs targeted in the clinical management of affective and psychotic disorders.
receptors were blocked by pretreatment with nonselective and selective opioid-receptor antagonists. This observation indicates the important role of the endogenous opioid system in the beneficial effects of the purinergic mechanism of antipsychotic action (Sikka et al., 2022). Trace Aminergic Interactions Trace amines are present in the mammalian brain in trace quantities. Since the discovery of monoamine oxidase inhibitors, the antipsychotic and antidepressant actions of these amines have been constantly studied in psychopharmacology. In humans, the most widely studied amines in this class include phenethylamines (phenethylamine, n-methylene-ethylamine, phenylethanolamine, and p-tyramine, 3-methoxytyramine, n-methyltyramine, m- and p-octopamine, and synephrine), thyronamines (3-iodothyronine), and tryptamines (tryptamine). In chemical orientation and metabolic function, these amines are similar in configuration to the classical amines. The interest in trace amines was largely absent until recently, when research on their possible interaction with the clinical effects of antipsychotic medications surfaced. These studies have also revolutionized psychopharmacological interests in trace amines by describing the trace amino acid receptors (TAARS). This discovery solidified the position of trace amines as important signaling molecules acting as neurotransmitters in the brain, although they are present in negligible quantities (Krasavin et al., 2022). Five TAARS, all G-protein coupled, have been discovered so far: TAAR1, TAAR2, TAAR5, TAAR6, and TAAR8. This hypothesis is largely supported by multiple pieces of evidence gathered from different studies. This evidence includes the observation that TAAR1 receptors are densely expressed
Antipsychotic and antidepressant actions mediated by purinergic mechanisms have also been widely studied in animal models of psychoses using rodents. Over the years, the common themes in this research are multiple reports of anxiolytic, antipsychotic, and antidepressant-like effects demonstrated by the adenosine- 2A blockers (Camargo et al., 2022). The research findings from Carmargo et al. also mentioned a few chemical interactions that directly modulate the efficiency of these antagonists in the delivery of these actions. For instance, the antidepressant- like effect of adenosine was diminished by pretreatment with nonselective blockers of adenosine-2A receptors (caffeine) and a selective adenosine-2A receptor blocker. The important highlights of this research also suggest a critical role of adenosine-serotonin interactions in the putative antidepressant- like effect of the adenosine-2A receptor ligands. By extension, the antipsychotic and antidepressant effects of the purinergic in the brain, particularly in the dorsal raphe nucleus (DRN) and VTA. TAAR1 ligands have also shown antidepressant- and antipsychotic-like effects in different animal model experiments using rodents and primates. TAAR1 ligands also appear to modulate monoamine neurotransmission, with some agonists of TAAR1 described as inhibiting significant ex vivo excitability of 5-HT and dopamine neurons in brain slices. Recently, there have been reports on a possible mechanism by which TAAR1 receptors influence the antipsychotic action of endogenous monoamines and atypical antidepressants. These reports have increased the focus on TAAR receptors as a possible target for future antidepressant and antipsychotic drugs. Based on the research evidence available today, it appears the antipsychotic actions of trace amines are largely linked to their interaction with the serotonin and dopaminergic system (Dedic et al., 2021). CLINICAL PRIMARY HEALTHCARE INTERVENTIONS IN PSYCHOPHARMACOLOGY Clinical interventions requiring the use of psychotropic medications are strictly dictated by guidelines based on research
which mandates adopting minimum healthcare requirements for nursing homes. This section of the course is designed to highlight the most widely adopted drug interventions in modern psychopharmacology. These interventions are largely based on clinical studies and surveys conducted to investigate the optimal dose, monitoring schedules, and side effects of these drugs in adults, children, the geriatric population, and special populations.
findings. This is important, considering the psychoactive properties of these drugs, their side effects, and potential withdrawal syndromes. A few legislative and clinical guidelines have been drafted around the world to guide the prescription and widespread use of psychotropic medications. A significant example is the Omnibus Budget Reconciliation Act of 1987 (also known as the Nursing Home Reform Act of 1987) from the U.S., Anxiolytic/Hypnotic Medications In the adult population, the most commonly prescribed anxiolytics/hypnotics are benzodiazepines. Of this class, the most prescribed drugs include alprazolam (Xanax), lorazepam (Ativan), clonazepam (Klonopin), diazepam (Valium), and temazepam (Restoril). Preliminary studies exploring the pharmacokinetics of these drugs indicated an increased magnitude of side effects of these drugs in adults. The most commonly reported side effects include sedation and psychomotor impairment (Estrela et al., 2020). Other than when strictly needed, long-term use of benzodiazepines is generally contraindicated in adults due to an increased risk of cognitive decline, poor functional
PSYCHOTROPIC MEDICATION IN ADULTS
autonomy, and addiction. In this population, hypnotics are generally prescribed for insomnia and are not recommended for long-term use. The most widely prescribed hypnotics include zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta) (as well as mirtazapine [Remeron, Remeron SolTab], trazodone [Desyrel], nortriptyline [Pamelor], temazepam, and gabapentin [Neurontin]). Table 1 summarizes the widely adopted prescription regimen for anxiolytics in adults.
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