• The Korean Journal of Physiology and Pharmacology
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• v.20 no.4
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• pp.407-414
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• 2016

This study was performed to investigate whether the spinal cholinergic and serotonergic analgesic systems mediate the relieving effect of electroacupuncture (EA) on oxaliplatin-induced neuropathic cold allodynia in rats. The cold allodynia induced by an oxaliplatin injection (6 mg/kg, i.p.) was evaluated by immersing the rat's tail into cold water ($4^{\circ}C$) and measuring the withdrawal latency. EA stimulation (2 Hz, 0.3-ms pulse duration, 0.2~0.3 mA) at the acupoint ST36, GV3, or LI11 all showed a significant anti-allodynic effect, which was stronger at ST36. The analgesic effect of EA at ST36 was blocked by intraperitoneal injection of muscarinic acetylcholine receptor antagonist (atropine, 1 mg/kg), but not by nicotinic (mecamylamine, 2 mg/kg) receptor antagonist. Furthermore, intrathecal administration of $M_2$ (methoctramine, $10{\mu}g$) and $M_3$ (4-DAMP, $10{\mu}g$) receptor antagonist, but not $M_1$ (pirenzepine, $10{\mu}g$) receptor antagonist, blocked the effect. Also, spinal administration of $5-HT_3$ (MDL-72222, $12{\mu}g$) receptor antagonist, but not $5-HT_{1A}$ (NAN-190, $15{\mu}g$) or $5-HT_{2A}$ (ketanserin, $30{\mu}g$) receptor antagonist, prevented the anti-allodynic effect of EA. These results suggest that EA may have a significant analgesic action against oxaliplatin-induced neuropathic pain, which is mediated by spinal cholinergic ($M_2$, $M_3$) and serotonergic ($5-HT_3$) receptors.

• The Korean Journal of Pain
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• v.37 no.1
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• v.14 no.2
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• pp.157-173
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• 2003

The history of pediatric psychopharmacology is very short and the research on safety, efficacy and side effects is preliminary and long-term effect on growth and maturation is not well known yet. Clinical findings have shown that the responses to antidepressants, antipsychotics, CNS stimulants and steroids in children and adolescents might be different from adult populations. Based on these findings, this paper reviewed three issues, Firstly, in developmental pharmacokinetics. the author discussed the developmental factors affecting drug absorption, distribution, protein-binding, metabolism and excretion. Secondly, in developmental pharmacodynamics, developmental characteristics of dopamine, serotonin, norepinephrine receptors and their clinical implications were reviewed. Lastly, in pharamcogenetic part, the clinical utility of pharmacogenetics, pharmacokinetic aspects of pharmacogenetics, the pharmacodynamic aspects of pharmacogenetics, the association studies of dopamine-related alleles in neuropsychiatric disorders such as attention-deficit hyperactivity disorders or Tourette’s disorders, pharmacogenetic studies dopamine-related alleles and the pharmacogenetic studies of serotonin-related alleles. Based on these preliminary research, future pharmacogenetic applications in childhood and adolescent psychiatry were also discussed.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.259-263
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• 1999

Nefazodone, a newer antidepressant is a phenylpiperazine derivative that inhibits the reuptake of both norepinephrine and serotonin, and antagonizes $5-HT_{2A}$ and ${\alpha}_1$ adrenergic receptors. Compared with SSRIs, nefazodone caused the fewer activating symptoms, adverse gastrointestinal effects(nausea, diarrhea, anorexia) and adverse effects of sexual function, but is associated with the more dizziness, dry mouth, constipation, visual disturbances and confusion. We report on 4 cases of visual disturbances and hallucinations in patients taking nefazodone. It is not certain what mechanisms mediated these side effects, but three mechanisms are possible. 1) Nefazodone, as a 5-HT2 antagonist, might induce visual disturbances. 2) mCPP, metabolite of nefazodone might contribute to the hallucination through action on 5-HT receptor. 3) Dopaminergic enhancing activity of nefazodone might cause hallucination. These case report raises the possibility that dose-related perceptual disturbances may exist with nefazodone. The fact emphasizes the need to pay close attention to all possible drug interactions, particularly in patients treated with multiple psychoactive agents, older patients, and patients with decreased hepatic function.

• The Korean Journal of Malacology
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• v.25 no.1
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• pp.15-22
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• 2009

Because it is known that bivalve hearts contain various modulatory systems activated by neuroendocrine substances, it was examined whether different classes of endogenous and synthetic drugs of neuroendocrinological importance can influence cardiac functions of the Pacific oyster Crassostrea gigas. Cholinergically active agents acetylcholine and carbachol increased heart rates while diminishing cardiac contractility. Adrenergically active substances norepinephrine (NE) and epinephrine (Epi) also induced heart rate increase and contractility decrease. An $\alpha_1$-adrenergic receptor-selective agonist phenyephrine (PE) failed to modulate either parameter. The Epi-induced heart rate increase and contractile depression were both blocked significantly by non-selective $\beta_1/\beta_2$-adrenergic antagonist propranolol. A $\beta_1$-selective antagonist atenolol prevented Epi-induced heart rate decrease but not the contractile depression, suggesting possible $\beta_2$ receptors for Epi-induced contractile depression. The three autacoids examined exerted discrete responses: histamine increased heart rate and depressed contraction; $\gamma$-amino-butyric acid increased both parameters; serotonin failed to change either parameter. The 5 piscine anesthetic agents examined, MS-222, benzocaine, quinaldine, urethane, pantocaine and pentobarbital, all failed to influence the cardiac function of oysters. Collectively, activities of neuroendocrinologically acting agents in mammals showed unexpected and distinct activities from those in mammalian cardiovascular systems. These results obtained from substances of different physiological functions can serve as a basis for understanding neuroendocrine control of the heart function in Pacific oyster.

• Korean journal of applied entomology
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• v.40 no.2
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• pp.155-196
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• 2001

Basically insect hormones include ecdysteroids (molting hormone), juvenile hormones, and neurohormones comprising neuropeptides and biogenic amines. This article reviewed their chemical structures and biological functions. The active molting hormone is 20-hydroxyecdysone in most insects but makisterone A in some other insects including the honey bee and several phytophagous hemipterans. Most insects use JH III, but lepidopterans JH I and II. Dipterans also use a different JH, so-called JH $B_3$(JH III bisepoxide) and we still do not know the exact chemical structure of JH utilized in hemipterans. Some other insects use methyl farnesoate or hydroxylated JH III analogues as their juvenile hormone. Most diverse pictures can be found in neurohormones (NH), especially in neuropeptides, in terms of their number and structure. There are more than 200 neuropeptides (NP), classified into more than 30 families, which structures have been identified, and more of them are expected to be reported in the near future, partly due to rapid development in molecular biological techniques and in analytical techniques. More than half of them are involved in controlling activity of visceral muscles. But function (s) of many NPs are not clarified yet, even though their amino acid sequences have been identified. It is partly due to the fact that a single NP may have multiple functions. Another interesting point is their gene structure, having many number of independent, active peptides in one gene, apparently working for similar or totally different functions. NH also includes amines, such as octopamine, dopamine, serotonin, etc. From now on, investigation will be concentrated on identifying their function (s) and receptors, and on possibilities of their utilization as control agents against pest insects.

• Sleep Medicine and Psychophysiology
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• v.2 no.2
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• pp.133-137
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• 1995

The author reviews current knowledge about what REM sleep is and where and how it is generated. REM sleep is the state in which our most vivid dreams occur. REM sleep is identified by the simultaneous presence of a desynchronized cortical EEG, an absence of activity in the antigravity muscles(atonia), and periodic bursts of rapid eye movements. Another characteristic phenomena of REM sleep are the highly synchronized hippocampal EEG of theta frequency and the ponto-geniculo-occipital(PGO) spike. All these phenomena can be explained in terms of changes in neuronal activity. Transection studies have determined that the pons is sufficient for generating REM sleep. Lesion studies have identified a small region in the lateral pontine tegmentum corresponding to lateral portions of the nucleus reticularis pontis oralis(RPO) and the region immediately ventral to the locus coeruleus, which is required for REM sleep. Unit recording studies have found a population of cells within this region that is selectively active in REM sleep. Cholinergic neurons of the giant cell field of pontine tegmentum(ETG), which is 'REM a sleep-on cells', has shown to be critically involved in the generation of REM sleep. Noradrenergic neurons of the locus coeruleus and serotonergic neurons of the dorsal raphe, which are called 'REM sleep-off cells', appear to act in a reciprocal manner to the cholinergic neurons. It is proposed that the periodic cessations of discharge of 'REM sleep-off cells' during REM sleep might be significant for the prevention of the desensitization of receptors of these neurons.

• Journal of Medicine and Life Science
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• v.18 no.3
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• pp.49-55
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• 2021

Atypical antipsychotics are more effective than typical antipsychotics and have fewer side effects such as tardive dyskinesia and extrapyramidal symptoms; therefore, prescriptions of atypical antipsychotics are increasing. However, recently, it has been reported that atypical antipsychotics have a higher incidence of diabetes, hyperglycemia, and obesity than typical antipsychotics. Atypical antipsychotics induce obesity-inhibiting appetite-related receptors such as serotonin and dopamine. Decreased exercise due to improving psychotic symptoms, and genetic characterictics can also cause weight gain. Hyperglycemia and hypoglycemia were another metabolic problem related to treatment with atypical antipsychotics. The mechanisms of hyperglycemia were mainly related obesity, decreased anorexigenic hormones, and increased insulin resistance in multiple organs. There are also reports that genes related to diabetes have an effect on the incidence of diabetes mellitus treated with atypical antipsychotics. On the other hand, although it is not clear why hypoglycemia occurs, it documented in case reports all over the world. There are more reports of atypical antipsychotics than typical antipsychotics and these are frequently reported in Asians. Further research on the mechanism of hypoglycemia related to atypical antipsychotics is strongly recommended.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.605-611
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• 2016

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine ($10{\sim}100{\mu}M$) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine ($30{\mu}M$), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-$HT_{2A}$ receptor inhibitor, indicating that ketamine facilitated the activation of 5-$HT_{2A}$ receptors. Anpirtoline and BW723C86, selective agonists of 5-$HT_{1B}$ and 5-$HT_{2B}$ receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-$HT_{2A}$ receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-$HT_{2A}$ receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.

• Asian-Australasian Journal of Animal Sciences
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• v.30 no.12
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• pp.1784-1795
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• 2017

Objective: The study examined the effect of intravenous administration of bacterial endotoxin-lipopolysaccharide (LPS) -on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). Methods: In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Results: Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. Conclusion: The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.