Serotoninergic Modulation of Basal Cardiovascular Responses and Responses Induced by Isotonic Extracellular Volume Expansion in Rats / Modulação Serotoninérgica de Respostas Cardiovasculares Basais e Induzidas pela Expansão Isotônica do Volume Extracelular em Ratos

Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

The putative catalytic role of higher serotonin bioavailability in the clinical response to exposure and response prevention in obsessive-compulsive disorder

Objective: Exposure and response prevention (ERP) is effective to treat obsessive-compulsive disorder (OCD), but the lack of tolerance to the aversion nature of exposure techniques results in a high drop-out rate. There have been reports of a generic stress endurance effect of serotonin (5-HT) in the central nervous system (CNS) which might be explained by suppression of defensive fixed action patterns. Previous studies have proposed that higher baseline 5-HT concentration and slow decrease in concentration during drug treatment of OCD were predictors of good clinical response to 5-HT reuptake inhibitors. The objective of this study was to investigate whether pre-treatment platelet rich plasma (PRP) 5-HT concentration is associated with latency of treatment response and final response to an ERP protocol for obsessive-compulsive disorder (OCD). Methods: Thirty adult and treatment-free OCD patients were included in an 8-week, 16-session ERP protocol. 5-HT concentration was determined at baseline and after treatment. Patients with a reduction ≥30% on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at the end of ERP were defined as responders. Results: A positive correlation between baseline 5-HT concentration and reduction of symptoms on the Y-BOCS was observed after 4 weeks. Baseline 5-HT concentration was not correlated with clinical response after 8 weeks of ERP, possibly due to the similar though delayed clinical response of patients with lower (compared to those with higher) baseline 5-HT concentration. Patients with higher 5-HT baseline concentration also showed more improvement in depressive symptoms with treatment. Conclusion: The present results partially support the hypothesis of a stress endurance effect of 5-HT in OCD patients. According to the literature, fast onset responders possibly have more or larger 5-HT containing neurons, higher endogenous 5-HT synthesis or lower monoamine oxidase activity; all these hypotheses remain to be investigated.

Selective 5-HT7 receptor agonists LP 44 and LP 211 elicit an analgesic effect on formalin-induced orofacial pain in mice

ABSTRACT The most recently identified serotonin (5-HT) receptor is the 5-HT7 receptor. The antinociceptive effects of a 5-HT7 receptor agonist have been shown in neuropathic and inflammatory animal models of pain. A recent study demonstrated the functional expression of 5-HT7 receptors in the substantia gelatinosa (SG) of the trigeminal subnucleus caudalis, which receives and processes orofacial nociceptive inputs. Objective To investigate the antinociceptive effects of pharmacological activation of 5-HT7 receptors on orofacial pain in mice. Material and Methods Nociception was evaluated by using an orofacial formalin test in male Balb-C mice. Selective 5-HT7 receptor agonists, LP 44 and LP 211 (1, 5, and 10 mg/kg), were given intraperitoneally 30 min prior to a formalin injection. A bolus of 10 µl of 4% subcutaneous formalin was injected into the upper lip of mice and facial grooming behaviors were monitored. The behavioral responses consisted of two distinct periods, the early phase corresponding to acute pain (Phase I: 0–12 min) and the late phase (Phase II: 12–30 min). Results LP 44 and LP 211 (1, 5, and 10 mg/kg) produced an analgesic effect with reductions in face rubbing time in both Phase I and Phase II of the formalin test. Conclusion Our results suggest that 5-HT7 receptor agonists may be promising analgesic drugs in the treatment of orofacial pain.

Effect of 5-HT7 receptor agonist on pyramidal neurons in the medial frontal cortex in a rat model of Parkinson's disease / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the activity of pyramidal neurons in the medial prefrontal cortex (mPFC) of normal and 6-OHDA-lesioned rats and the responses of the neurons to 5-hydroxytryptamine-7 (5-HT(7)) receptor stimulation.</p><p><b>METHODS</b>The changes in spontaneous firing of the pyramidal neurons in the mPFC in response to 5-HT(7) receptor stimulation were observed by extracellular recording in normal and 6-OHDA-lesioned rats.</p><p><b>RESULTS</b>Both systemic and local administration of 5-HT(7) receptor agonist AS 19 resulted in 3 response patterns (excitation, inhibition and no change) of the pyramidal neurons in the mPFC of normal and 6-OHDA-lesioned rats. In normal rats, the predominant response of the pyramidal neurons to AS 19 stimulation was excitatory, and the inhibitory effect of systemically administered AS 19 was reversed by GABAA receptor antagonist picrotoxinin. In the lesioned rats, systemic administration of AS 19 also increased the mean firing rate of the pyramidal neurons, but the cumulative dose for producing excitation was higher than that in normal rats. Systemic administration of AS 19 produced an inhibitory effect in the lesioned rats, which was partially reversed by picrotoxinin. Local administration of AS 19 at the same dose did not change the ?ring rate of the neurons in the lesioned rats.</p><p><b>CONCLUSION</b>The activity of mPFC pyramidal neurons is directly or indirectly regulated by 5-HT7 receptor, and degeneration of the nigrostriatal pathway leads to decreased response of these neurons to AS 19.</p>

Effect of 5-HT1A receptors in the hippocampal DG on active avoidance learning in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effects of serotonin (5-HTIA) receptors in the hippocampal dentate gyrus (DG) on active avoidance learning in rats.</p><p><b>METHODS</b>Totally 36 SD rats were randomly divided into control group, antagonist group and agonist group(n = 12). Active avoidance learning ability of rats was assessed by the shuttle box. The extracellular concentrations of 5-HT in the DG during active avoidance conditioned reflex were measured by microdialysis and high performance liquid chromatography (HPLC) techniques. Then the antagonist (WAY-100635) or agonist (8-OH-DPAT) of the 5-HT1A receptors were microinjected into the DG region, and the active avoidance learning was measured.</p><p><b>RESULTS</b>(1) During the active avoidance learning, the concentration of 5-HT in the hippocampal DG was significantly increased in the extinction but not establishment in the conditioned reflex, which reached 164.90% ± 26.07% (P <0.05) of basal level. (2) The microinjection of WAY-100635 (an antagonist of 5-HT1A receptor) into the DG did not significantly affect the active avoidance learning. (3) The microinjection of 8-OH-DPAT(an agonist of 5-HT1A receptor) into the DG significantly facilitated the establishment process and inhibited the extinction process during active avoidance conditioned reflex.</p><p><b>CONCLUSION</b>The data suggest that activation of 5-HT1A receptors in hipocampal DG may facilitate active avoidance learning and memory in rats.</p>

A cell membrane chromatography method for screening 5-HT receptor agonists from drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix / 中国中药杂志

Migraine is one of the common and frequently encountered diseases. The study proves that 5-hydroxytryptamine (5-HT) receptor, plays an important role in the occurrence of migraine. Rat striatum was used for preparation of the cell membrane stationary phase (CMSP) in our experiments. The cell membrane chromatography (CMC)-offline-HPLC system was applied to specifically recognize the components from the drug pair of Chuanxiong Rhizoma and Angelicae Dahuricae Radix, which interact with the receptors on CMSP. The dissociation equilibrium constant (KD) was measured in a rat striatum/CMC system, performed by continuously pumping sumatriptan, a 5-HT1D agonist, ranging from 2.42 x 10(-8) to 4.84 x 10(-7) mol · L(-1) through a CMC column, and the capacity factors (k') were recorded. The KD value obtained from the model was (4.59 ± 0.33) x 10(-6) mol · L(-1) for imperatorin, and the rat model of migraine induced by nitroglycerin was applied to validate the pharmacological effects of the drug pair. The results indicated that the CMC method could be a quick and efficient way for characterizing the drug-receptor interactions in vitro.

Emerging Pharmacologic Therapies for Constipation-predominant Irritable Bowel Syndrome and Chronic Constipation

Irritable bowel syndrome with constipation and chronic functional constipation are common digestive disorders that negatively impact quality of life and account for billions of dollars in health care costs. Related to the heterogeneity of pathogenesis that underlie these disorders and the failure of symptoms to reliably predict underlying pathophysiology, traditional therapies provide relief to only a subset of affected individuals. The evidence surrounding new and emerging pharmacologic treatments, which include both luminally and systemically acting drugs, is discussed here. These include agents such as lubiprostone, bile acid modulations, guanylate cyclase-C receptor agonists, serotonin receptor modulators and herbal therapies.

Serotonin syndrome associated with linezolid

Serotonin syndrome (SS) is a potentially life-threatening drug reaction characterized by mental status change, increased neuromuscular tone, and autonomic instability. Linezolid, an oxazolidinone antibacterial agent, is widely used in general hospitals; however, it interacts with some serotonin agonists and may cause SS. We report a case of SS caused by linezolid, without the concomitant use of serotonin agonist. A 72-year-old patient was admitted due to recurrent wound infection of his left ankle. He developed fever, skin rash, and renal function deterioration, and blood eosinophils and liver enzymes increased after administration of vancomycin. The antibiotic was changed to linezolid against methicillin-resistant Staphylococcus aureus. Four days later, he developed agitation, fever, increased blood pressure, and tachycardia. There were no abnormal findings in laboratory and image tests, including brain and chest computed tomography suggesting the cause of his symptoms. He had not taken any serotonin agonists, including serotonin uptake inhibitors and monoamineoxidase-inhibiting antidepressants. When administration of linezolid was stopped, his symptoms improved within 24 hours and fully recovered within 2 days without additional treatments.

Current Issues in Functional Dyspepsia / 대한소화기학회지

Functional dyspepsia is one of the most common gastrointestinal disorders encountered in clinical practice. Functional dyspepsia is currently defined by Rome III criteria as the chronic dyspeptic symptoms (postprandial fullness, early satiety, epigastric pain or burning) in the absence of underling structural or metabolic disease that readily explain the symptoms. According to the Rome III consensus, functional dyspepsia can be subdivided into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Although the Rome III criteria have been published more than 8 years ago, not much effort has been put into validating these criteria and direct scientific evidence supporting the validity of the subdividing functional dyspepsia into PDS and EPS are lacking. This article is intended to review the validity of the Rome III criteria on the subdivisions of functional dyspepsia, i.e. PDS and EPS. The impact of sleep disorder, Helicobacter pylori-associated dyspepsia, and the emerging drug therapies in functional dyspepsia will also be discussed in this article.

Human umbilical artery smooth muscle exhibits a 2-APB-sensitive capacitative contractile response evoked by vasoactive substances and expresses mRNAs for STIM, Orai and TRPC channels

After depletion of intracellular Ca2+ stores the capacitative response triggers an extracellular Ca2+ influx through store-operated channels (SOCs) which refills these stores. Our objective was to explore if human umbilical artery smooth muscle presented this response and if it was involved in the mechanism of serotonin- and histamine-induced contractions. Intracellular Ca2+ depletion by a Ca2+-free extracellular solution followed by Ca2+ readdition produced a contraction in artery rings which was inhibited by the blocker of Orai and TRPC channels 2-aminoethoxydiphenyl borate (2-APB), suggesting a capacitative response. In presence of 2-APB the magnitude of a second paired contraction by serotonin or histamine was significantly less than a first one, likely because 2-APB inhibited store refilling by capacitative Ca2+ entry. 2-APB inhibition of sarcoplasmic reticulum Ca2+ release was excluded because this blocker did not affect serotonin force development in a Ca2+-free solution. The PCR technique showed the presence of mRNAs for STIM proteins (1 and 2), for Orai proteins (1, 2 and 3) and for TRPC channels (subtypes 1, 3, 4 and 6) in the smooth muscle of the human umbilical artery. Hence, this artery presents a capacitative contractile response triggered by stimulation with physiological vasoconstrictors and expresses mRNAs for proteins and channels previously identified as SOCs.

Hiccup: Mystery, Nature and Treatment

Hiccup is the sudden onset of erratic diaphragmatic and intercostal muscle contraction and immediately followed by laryngeal closure. The abrupt air rush into lungs elicits a "hic" sound. Hiccup is usually a self-limited disorder; however, when it is prolonged beyond 48 hours, it is considered persistent whereas episodes longer than 2 months are called intractable. A reflex arc involving peripheral phrenic, vagal and sympathetic pathways and central midbrain modulation is likely responsible for hiccup. Accordingly, any irritant in terms of physical/chemical factors, inflammation, neoplasia invading the arc leads to hiccups. The central causes of hiccup include stroke, space occupying lesions and injury etc, whereas peripheral causes include lesions along the arc such as tumors, myocardial ischemia, herpes infection, gastroesophageal reflux disease and applied instrumentations on human body etc. Besides, various drugs (eg, anti-parkinsonism drugs, anesthetic agents, steroids and chemotherapies etc) are the possible etiology. An effective treatment of persistent hiccup may be established upon the correct diagnosis of lesion responsible for the serious event. The pharmacotherapy of hiccup includes chlorpromazine, gabapentin, baclofen, serotonergic agonists, prokinetics and lidocaine. Non-pharmacological approaches such as nerve blockade, pacing, acupuncture and measures to hold breathing are also successful. Finally, alternative medicines and remedies are convenient to treat hiccups with uncertain effect. In conclusions, hiccup is likely to result from lesions involving the hiccup reflex arc. The lesion may need to be localized correctly for ablative treatment in patients with intractable hiccup. Apart from lesion ablation, drugs acting on reflex arc may be effective, while some other conventional measures may also be tried.

Central 5-HT2A receptors modulate the vagal bradycardia in response to activation of the von Bezold-Jarisch reflex in anesthetized rats

Activation of 5-hydroxytryptamine (5-HT) 5-HT1A, 5-HT2C, 5-HT3, and 5-HT7 receptors modulates the excitability of cardiac vagal motoneurones, but the precise role of 5-HT2A/2B receptors in these phenomena is unclear. We report here the effects of intracisternal (ic) administration of selective 5-HT2A/2B antagonists on the vagal bradycardia elicited by activation of the von Bezold-Jarisch reflex with phenylbiguanide. The experiments were performed on urethane-anesthetized male Wistar rats (250-270 g, N = 7-9 per group). The animals were placed in a stereotaxic frame and their atlanto-occipital membrane was exposed to allow ic injections. The rats received atenolol (1 mg/kg, iv) to block the sympathetic component of the reflex bradycardia; 20-min later, the cardiopulmonary reflex was induced with phenylbiguanide (15 µg/kg, iv) injected at 15-min intervals until 3 similar bradycardias were obtained. Ten minutes after the last pre-drug bradycardia, R-96544 (a 5-HT2A antagonist; 0.1 µmol/kg), SB-204741 (a 5-HT2B antagonist; 0.1 µmol/kg) or vehicle was injected ic. The subsequent iv injections of phenylbiguanide were administered 5, 20, 35, and 50 min after the ic injection. The selective 5-HT2A receptor antagonism attenuated the vagal bradycardia and hypotension, with maximal effect at 35 min after the antagonist (pre-drug = -200 ± 11 bpm and -42 ± 3 mmHg; at 35 min = -84 ± 10 bpm and -33 ± 2 mmHg; P < 0.05). Neither the 5-HT2B receptor antagonists nor the vehicle changed the reflex. These data suggest that central 5-HT2A receptors modulate the central pathways of the parasympathetic component of the von Bezold-Jarisch reflex.

Serotonina e controle hipotalâmico da fome: uma revisão / Serotonin and hypothalamic control of hunger: a review

Este trabalho revisa a participação do sistema serotonérgico no controle da ingestão de alimentos e saciedade. É de grande interesse compreender a relevância desse sistema para o controle fisiológico do balanço energético e da obesidade. Mais de 35 anos de pesquisas sugerem que a serotonina (5-HT) desempenha um importante papel na saciedade. Assim, o sistema serotonérgico tem sido um alvo viável para o controle de peso. A 5-HT apresenta controle sobre a fome e a saciedade através de diversos receptores, com diferentes funções. O receptor 5-HT2C parece ser o mais importante na relação entre ingestão alimentar e balanço energético. Nesta revisão serão discutidos os mecanismos do sistema serotonérgico envolvidos no controle da ingestão de alimentos e saciedade.

This paper reviews involvement of the serotonergic system in the control of food intake and satiety. It is of great interest to understand the relevance of this system for physiological control of energy balance and obesity. Over 35 years of research suggest that serotonin (5-HT) plays an important role in satiety. Thus, the serotonergic system has been a viable target for weight control. The 5-HT has control over hunger and satiety through different receptors with distinct functions. The 5-HT2C receptor may be more important in the relationship between food intake and energy balance. This review will discuss the mechanisms of the serotonergic system involved in the control of food intake and satiety.

Characteristics of 5-Hydroxytryptamine Receptors Involved in Contraction of Feline Ileal Longitudinal Smooth Muscle

A number of studies have demonstrated that 5-hydroxytryptamine (5-HT) can induce muscle contraction or relaxation response and enhance secretion in the gastrointestinal tract via a multiplicity of 5-HT receptor subtypes. In the present study, we investigated the pharmacological characterization of the 5-HT-induced contractile response in longitudinal smooth muscle isolated from the feline ileum. Addition of 5-HT into muscle chambers enhanced the basal tone and spontaneous activity in a concentration-dependent manner. The neurotoxin tetrodotoxin did not alter the 5-HT-induced contraction of the longitudinal muscles. Neither atropine nor guanethidine affected the contraction. The 5-HT agonists, 5-methylserotonin hydrochloride and mosapride, also evoked concentration-dependent contractions. The 5-HT-induced contraction was enhanced by the 5HT2 receptor antagonist ketanserin and the 5-HT3 receptor antagonist ondansetron but was inhibited by the 5-HT1 receptor antagonist methysergide and 5-HT4 receptor antagonist GR113808. These results indicate that 5-HT1 and 5-HT4 receptors may mediate the contraction of the 5-HT-induced response and 5-HT2 and 5-HT3 receptors may mediate 5-HT-induced relaxation in feline ileal longitudinal smooth muscles.

[Study of buspirone effect on motor behavior in rats with parkinson disease caused by reserpine]

Death of dopaminergic neurons, in substantia nigra pars compacta, results in exsanguinations of neurotransmitter dopamine in corpus striatum and motor symptoms of Parkinson disease. However, deterioration of non-dopaminergic neurons, such as serotonergic and noradrenergic neurons, became one of fixed truths of Parkinson disease. It was suggested that these neurons deterioration has a role in motor symptoms, in addition to non-motor symptoms, such as depression, imperceptions and sleep disorders. So, the aim of research was testing Buspirone effect, a partial agonist of 5-HT[1A] auto serotonergic receptors, for improvement of Parkinsons' symptoms in Wister adult albino male rats with Parkinson disease caused by Reserpine [3 mg/kg]. And study of Buspirone effect on L-DOPA therapeutic activity and its important for dyskinesia treatment resulted from long term therapy with L-DOPA. The current study illustrated that low dosages of Buspirone [0.25, 1, 3 and 6 mg/Kg] improved the affected rats' movement, whereas high dosage [10 mg/kg] didn't improve the movement, by comparing these groups with control group which has injected with injected water. Also, this study revealed that Buspirone lows the therapeutic activity of L-DOPA, by comparing the motor behavior of affected groups, which treated with Buspirone [3, 6 and 10 mg/kg]+L-DOPA [100 mg/kg], with that treated only with 100 mg/kg of L-DOPA. As conclusion, our study appears Buspirone efficiency to improve the symptoms of Parkinson disease in animal samples, as it gives an area for clinical experiments for testing the effect of Buspirone [currently used for anxiety treatment] on Parkinson disease's symptoms, in patients suffering from side effects of L-DOPA

Hypophagic and hypolocomotive effects of metachloro phenyl piperazine in rats treated with theophylline and caffeine

Long term intake of coffee is known to produce anxiety and suppression of appetite. 5- hydroxytryptamine [5-HT] acting via 5-HT-2C receptors elicits anorexia and anxiety. The present study is design to monitor metachloro phenyl piperazine [m-CPP] at a dose of 3mg/ml/kg, induces hypophagia and hypolocomotion in rats taking a solution of caffeine [a component of coffee and tea] or theophylline [a component of tea] as a sole source of water. We found that hypophagic and hypolocomotive effects of m-CPP were attenuated in theophylline but not in caffeine treated animals suggesting that long term intake of theophylline may, attenuate anorexiogenic and anxiogenic effects of 5-HT. A possible role of 5-HT-2C receptors in the modulation of anxiety and appetite in people drinking coffee or tea discussed

Effects of 5-hydroxytryptamine and 5-hydroxytryptamine 2A/2C agonist on the genioglossus activity and sleep apnea in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>5-Hydroxytryptamine (5-HT) is a common neurotransmitter in the brain which plays an important role in the pathogenesis of sleep apnea. Dysfunction of 5-HT and 5-HT(2) receptors may lead to the collapse of the upper airway and the instability of respiratory control, which in turn produce apnea. Genioglossus (GG) is one of the most important oropharyngeal muscles maintaining the upper airway open. The present study aimed to investigate the effects of 5-HT and 5-HT(2) receptor on GG activity and the sleep apnea in Sprague-Dawley (SD) rats.</p><p><b>METHODS</b>Microinjection probes were placed within the fourth ventricle of sixteen SD rats. After recovery for a week, the electromyogram (EMG) of GG was recorded in the anesthetized and vagotomized rats. The changes of GG activity before and after the microinjection of 5-HT or 5-HT(2A/2C) agonist -2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) were observed. Probes were also laid in another eight SD rats. Electroencephalogram (EEG), EMG of neck muscle and respiration were recorded at the same time a week later. The effects of DOI on the occurrence of sleep apnea were explored.</p><p><b>RESULTS</b>Both 5-HT and DOI significantly enhanced the activity of GG just 3 minutes after the completion of injection. The effect of 5-HT disappeared quickly and the effect of DOI lasted for more than 27 minutes. DOI also significantly decreased the post-sigh apnea index in non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep and decreased the spontaneous apnea index only in NREM sleep (P < 0.05, respectively).</p><p><b>CONCLUSION</b>5-HT and 5-HT(2A/2C) system correlated closely with the pathogenesis of the sleep apnea syndrome and 5-HT receptors may become the target of the drug treatment.</p>

Migraine in the triptan era: progresses achieved, lessons learned and future developments / Migrânea na era dos triptanos: progressos alcançados, lições aprendidas e desenvolvimentos futuros

Triptans, serotonin 5-HT1B/1D receptor agonists, more than revolutionizing the treatment of migraine, stimulated also ground breaking research that provided insights into the anatomy, physiology, and molecular pharmacology of migraine. This knowledge, in turn, is stimulating research on new mechanisms of action for the treatment of migraine. Accordingly, it is opportune to critically review the main advances in migraine science that happened in the triptan era. Herein we first review and conceptualize some of the progresses achieved in migraine science during the triptan era. We then review the class of the triptans - mechanism of action and clinical evidence. We close by briefly discussing the class of CGRP receptor antagonists, which is currently being developed for the acute treatment of migraine.

Os triptanos, agonistas serotoninérgicos 5-HT1B/1D, revolucionaram o tratamento da migrânea promovendo pesquisas que evidenciaram aspectos da anatomia, fisiologia e farmacologia molecular deste tipo prevalente de cefaléia primária. Esse conhecimento, por sua vez vem estimulando ainda mais a descoberta de novos mecanismos de ação para drogas anti-migranosas. Assim, é oportuno rever de forma crítica, os maiores avanços na ciência das cefaléias ocorridos durante a era dos triptanos. Inicialmente reveremos e conceituaremos alguns dos progressos obtidos nesta fase seguido de uma revisão profunda dos mecanismos de ação e evidências clínicas para o uso desta classe de fármacos. Finalmente, discutiremos a nova classe dos antagonistas dos receptores do peptideo geneticamente relacionado à calcitonina (CGRP) atualmente em desenvolvimento.

[Caries status in asthmatic children receiving anti-asthma inhalers]

Asthma is known as a probable risk factor for dental caries; however there is some controversy in this issue. Present study is designated to evaluate the caries status in asthmatics compared to non asthmatic controls. In addition probable factors and co-varieties associated with dental health were also investigated. Forty five asthmatics and 46 healthy controls aged 6 to 12, entered this case-control study. There was a history of asthmatic drugs for at least one year including inhalators of beta-agonist, Corticosteroid or both. DMFS Index recorded according to visual- tactile method. Stimulated saliva was obtained and microbial count performed as CFU/ml for S. Mutans and Lacto Bacilli. Data analysis performed according to t-test, Mann-Whitney, Kendall's Rank Correlation and Ridge Regression. Mean DMFS Index was 3.98 +/- 2.53 in asthmatics and 4.3 +/- 2.81 in healthy controls. The difference was not significant caries. Final Ridge Regression showed significant correlation between drug regimen and caries [P=0.001, r=0.76]. Those received beta agonist along with protective corticosteroid had significantly less caries compare to beta agonist alone [P<0.001]. S. Mutans count revealed significantly higher in controls. Lactobacilli count was not significantly different. DMFS index was not significantly different. Inhaled corticosteroids in asthmatics leads to better control of disease process, and reduce dental caries maybe because of reduced beta 2-agonist consumption as a potent xerostomic