Sympathomimetic agents are a group of chemical compounds that are able to activate the sympathetic nervous system either directly via adrenergic receptors or indirectly by increasing endogenous catecholamine levels or mimicking their intracellular signaling pathways. Compounds from this group, both used therapeutically or abused, comprise endogenous catecholamines (such as adrenaline and noradrenaline), synthetic amines (e.g., isoproterenol and dobutamine), trace amines (e.g., tyramine, tryptamine, histamine and octopamine), illicit drugs (e.g., ephedrine, cathinone, and cocaine), or even caffeine and synephrine. In addition to the effects triggered by stimulation of the sympathetic system, the discovery of trace amine associated receptors (TAARs) in humans brought new insights about their sympathomimetic pharmacology and toxicology. Although synthetic sympathomimetic agents are mostly seen as toxic, natural sympathomimetic agents are considered more complacently in the terms of safety in the vision of the lay public. Here, we aim to discuss the pharmacological and mainly toxicological aspects related to sympathomimetic natural agents, in particular of trace amines, compounds derived from plants like ephedra and khat, and finally cocaine. The main purpose of this review is to give a scientific and updated view of those agents and serve as a reminder on the safety issues of natural sympathomimetic agents most used in the community.
- Keywords
- adrenaline, cathinone, cocaine, ephedrine, trace amines,
- MeSH
- Amines MeSH
- Cocaine * pharmacology MeSH
- Humans MeSH
- Norepinephrine MeSH
- Sympathomimetics * pharmacology MeSH
- Tyramine pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
- Names of Substances
- Amines MeSH
- Cocaine * MeSH
- Norepinephrine MeSH
- Sympathomimetics * MeSH
- Tyramine MeSH
BACKGROUND: The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO2) and autoregulatory capacity (CAR) remains unknown. METHODS: Prospective cohort study of blinded rScO2 measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO2, mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. RESULTS: In 89 potentially eligible HIP trial patients with rScO2 measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO2 was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. CONCLUSIONS: Dopamine had no effect on rScO2 compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. IMPACT: Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.
- MeSH
- Arterial Pressure * drug effects MeSH
- Biomarkers blood MeSH
- Time Factors MeSH
- Dopamine therapeutic use MeSH
- Gestational Age MeSH
- Homeostasis MeSH
- Hypotension blood drug therapy mortality physiopathology MeSH
- Cerebral Intraventricular Hemorrhage mortality physiopathology MeSH
- Infant MeSH
- Infant Mortality MeSH
- Oxygen blood MeSH
- Humans MeSH
- Hospital Mortality MeSH
- Hypoxia, Brain blood mortality physiopathology MeSH
- Cerebrovascular Circulation * MeSH
- Infant, Extremely Premature * MeSH
- Prospective Studies MeSH
- Oxygen Saturation * MeSH
- Sympathomimetics therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
- Randomized Controlled Trial MeSH
- Geographicals
- Europe MeSH
- Names of Substances
- Biomarkers MeSH
- Dopamine MeSH
- Oxygen MeSH
- Sympathomimetics MeSH
- MeSH
- Epinephrine pharmacology MeSH
- Atrial Natriuretic Factor pharmacology MeSH
- Pulmonary Disease, Chronic Obstructive metabolism therapy MeSH
- Hypoxia metabolism MeSH
- Fatty Acids, Nonesterified metabolism MeSH
- Middle Aged MeSH
- Humans MeSH
- Lipolysis * drug effects MeSH
- Microdialysis MeSH
- Oxygen Inhalation Therapy MeSH
- Subcutaneous Fat, Abdominal drug effects metabolism MeSH
- Severity of Illness Index MeSH
- Sympathomimetics pharmacology MeSH
- Adipose Tissue metabolism MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Letter MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Epinephrine MeSH
- Atrial Natriuretic Factor MeSH
- Fatty Acids, Nonesterified MeSH
- Sympathomimetics MeSH
The colorectum (late distal colon) is innervated by the sympathetic nervous system, and many colorectal diseases are related to disorders of the sympathetic nervous system. The sympathetic regulation of colorectal ion transport is rarely reported. The present study aims to investigate the effect of norepinephrine (NE) in the normal and catecholamine-depleted condition to clarify the regulation of the sympathetic adrenergic system in ion transport in the rat colorectum. NE-induced ion transport in the rats colorectum was measured by short-circuit current (I(sc)) recording; the expression of beta-adrenoceptors and NE transporter (NET) were quantified by real-time PCR, and western blotting. When the endogenous catecholamine was depleted by reserpine, the baseline I(sc) in the colorectum was increased significantly comparing to controls. NE evoked downward deltaI(sc) in colorectum of treated rats was 1.8-fold of controls. The expression of beta(2)-adrenoceptor protein in the colorectal mucosa was greater than the control, though the mRNA level was reduced. However, NET expression was significantly lower in catecholamine-depleted rats compared to the controls. In conclusion, the sympathetic nervous system plays an important role in regulating basal ion transport in the colorectum. Disorders of sympathetic neurotransmitters result in abnormal ion transport, beta-adrenoceptor and NET are involved in the process.
- MeSH
- Receptors, Adrenergic, beta-2 genetics metabolism MeSH
- Time Factors MeSH
- Epithelial Cells metabolism MeSH
- Adrenergic Uptake Inhibitors pharmacology MeSH
- Ion Transport MeSH
- Colon innervation metabolism MeSH
- Membrane Potentials MeSH
- RNA, Messenger metabolism MeSH
- Norepinephrine metabolism pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Norepinephrine Plasma Membrane Transport Proteins genetics metabolism MeSH
- Intestinal Mucosa innervation metabolism MeSH
- Sympathetic Nervous System drug effects physiology MeSH
- Sympathomimetics pharmacology MeSH
- In Vitro Techniques MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Receptors, Adrenergic, beta-2 MeSH
- Adrenergic Uptake Inhibitors MeSH
- RNA, Messenger MeSH
- Norepinephrine MeSH
- Norepinephrine Plasma Membrane Transport Proteins MeSH
- Slc6a2 protein, rat MeSH Browser
- Sympathomimetics MeSH
The aim of the present study was to determine effects of methamphetamine (MA) exposure and cross-fostering on thermal nociceptive thresholds in different estrous phases in adult female rats. Rat mothers were exposed daily to injection of MA (5 mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Dams without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised four pups of her own and eight pups from the mothers with the other two treatments. Offspring females were tested in adulthood (85-90 days) for thermal nociception as latency [s] of withdrawal reaction of forelimbs, hind limbs, and tail. Our results showed that prenatal MA exposure did not affect the nociception in adulthood, while postnatal MA exposure (i.e., MA administration to lactating mothers) had pro-nociceptive effects. The effect of postnatal MA exposure was apparent in both, fore- and hind limbs, while the latency to tail withdrawal reaction was the same among the groups. In addition, the pro-nociceptive effect of postnatal MA exposure did not depend on estrous cycle. This study indicates that postnatal but not prenatal exposure to MA affects nociception in adult female rats. However, it is still not clear whether the pro-nociceptive effect of postnatal MA exposure is linked to direct action of MA on neuronal organization, or to indirect action of MA mediated by impaired maternal care.
- MeSH
- Diestrus drug effects MeSH
- Injections, Subcutaneous MeSH
- Rats MeSH
- Methamphetamine toxicity MeSH
- Neurons drug effects MeSH
- Animals, Newborn physiology MeSH
- Rats, Wistar MeSH
- Pain Threshold drug effects MeSH
- Proestrus drug effects MeSH
- Reaction Time drug effects MeSH
- Sympathomimetics toxicity MeSH
- Pregnancy MeSH
- Age Factors MeSH
- Thermosensing drug effects MeSH
- Prenatal Exposure Delayed Effects physiopathology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Methamphetamine MeSH
- Sympathomimetics MeSH
This experiment tested the effect of risperidone on the sympathetic and thermogenic effects induced by orexin A. The firing rates of sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colon temperatures and heart rate were monitored in urethane-anesthetized male Sprague-Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 2 hours after the injection. The same variables were monitored in rats with an intraperitoneal administration of risperidone (50 mg/kg bw), injected 30 min before the orexin administration. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate. This increase is enhanced by the injection of risperidone. These findings suggest that risperidone elevates the responses due to orexin, probably through an involvement of serotoninergic and dopaminergic pathways, which are affected by risperidone. Furthermore, we suggested the name "hyperthermine A" as additional denomination of "orexin A" by considering the strong influence of this neuropeptide on body temperature.
- MeSH
- Adrenergic Fibers drug effects MeSH
- Action Potentials MeSH
- Antipsychotic Agents administration & dosage pharmacology MeSH
- Time Factors MeSH
- Adipose Tissue, Brown innervation MeSH
- Hyperthermia, Induced * MeSH
- Injections, Intraperitoneal MeSH
- Injections, Intraventricular MeSH
- Intracellular Signaling Peptides and Proteins * MeSH
- Rats MeSH
- Neuropeptides * MeSH
- Orexins MeSH
- Rats, Sprague-Dawley MeSH
- Risperidone administration & dosage pharmacology MeSH
- Heart Rate drug effects MeSH
- Sympathomimetics * MeSH
- Drug Synergism MeSH
- Body Temperature drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antipsychotic Agents MeSH
- HCRT protein, human MeSH Browser
- Intracellular Signaling Peptides and Proteins * MeSH
- Neuropeptides * MeSH
- Orexins MeSH
- Risperidone MeSH
- Sympathomimetics * MeSH
- MeSH
- Antihypertensive Agents administration & dosage MeSH
- Adult MeSH
- Pheochromocytoma diagnostic imaging drug therapy surgery MeSH
- Hypertension drug therapy MeSH
- Hypotension prevention & control MeSH
- Injections, Intravenous MeSH
- Blood Pressure drug effects MeSH
- Humans MeSH
- Adrenal Gland Neoplasms diagnostic imaging drug therapy surgery MeSH
- Nitroprusside administration & dosage MeSH
- Norepinephrine administration & dosage MeSH
- Tomography, X-Ray Computed MeSH
- Sympathomimetics administration & dosage MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Case Reports MeSH
- Names of Substances
- Antihypertensive Agents MeSH
- Nitroprusside MeSH
- Norepinephrine MeSH
- Sympathomimetics MeSH
This experiment tested the effect of clozapine on the sympathetic and thermogenic effects induced by orexin A. The firing rates of the sympathetic nerves to interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures were monitored in urethane-anesthetized male Sprague-Dawley rats before and for 5 h after an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle. The same procedure was carried out in rats treated with orexin A plus an intraperitoneal administration of clozapine (8 mg/kg bw), an atypical antipsychotic that is largely used in the therapy of schizophrenia. The same variables were monitored in rats with clozapine alone. A group of rats with saline injection served as control. The results show that orexin A increases the sympathetic firing rate, IBAT and colonic temperatures. Clozapine blocks completely the reactions due to orexin A. These findings suggest that clozapine influences strongly the thermogenic role of orexin A. Furthermore, the remarkable hyperthermic role played by orexin A is confirmed.
- MeSH
- Action Potentials drug effects physiology MeSH
- Serotonin Antagonists administration & dosage MeSH
- Drug Combinations MeSH
- Adipose Tissue, Brown drug effects innervation physiology MeSH
- Injections, Intraperitoneal MeSH
- Intracellular Signaling Peptides and Proteins administration & dosage MeSH
- Clozapine administration & dosage MeSH
- Rats MeSH
- Neuropeptides administration & dosage MeSH
- Orexins MeSH
- Rats, Sprague-Dawley MeSH
- Sympathetic Nervous System drug effects physiology MeSH
- Sympathomimetics administration & dosage MeSH
- Body Temperature drug effects physiology MeSH
- Thermogenesis drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Serotonin Antagonists MeSH
- Drug Combinations MeSH
- HCRT protein, human MeSH Browser
- Intracellular Signaling Peptides and Proteins MeSH
- Clozapine MeSH
- Neuropeptides MeSH
- Orexins MeSH
- Sympathomimetics MeSH
The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.
- MeSH
- Epinephrine administration & dosage MeSH
- Adrenergic beta-Agonists administration & dosage MeSH
- Adrenergic alpha-Antagonists administration & dosage MeSH
- Receptors, Adrenergic, alpha-2 metabolism MeSH
- Adult MeSH
- Phentolamine administration & dosage MeSH
- Glycerol blood MeSH
- Glucose Clamp Technique MeSH
- Hyperinsulinism metabolism MeSH
- Insulin blood MeSH
- Isoproterenol administration & dosage MeSH
- Humans MeSH
- Lipolysis drug effects physiology MeSH
- Microdialysis MeSH
- Subcutaneous Tissue drug effects metabolism MeSH
- Sympathomimetics administration & dosage MeSH
- Adipose Tissue drug effects metabolism MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Controlled Clinical Trial MeSH
- Clinical Trial MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Epinephrine MeSH
- Adrenergic beta-Agonists MeSH
- Adrenergic alpha-Antagonists MeSH
- Receptors, Adrenergic, alpha-2 MeSH
- Phentolamine MeSH
- Glycerol MeSH
- Insulin MeSH
- Isoproterenol MeSH
- Sympathomimetics MeSH
Streptozotocin (STZ) is used to induce experimental diabetes in animals and is also applied for the treatment of patients with insulinoma. The aim of the present work was to investigate the direct effect of STZ on lipolysis in isolated rat adipocytes. After the isolation, the cells were incubated in a Krebs-Ringer buffer of pH 7.4, at the temperature 37 degrees C for 90 min with different concentrations of STZ: 0.5, 1 or 2 mmol/l. STZ caused a significant rise in basal values (99%, 199%, and 377%, respectively) and epinephrine-stimulated (1 micromol/l) lipolysis (15%, 24% and 46%, respectively). Augmentation of basal lipolysis by STZ was neither restricted by insulin (1 nmol/l) nor by H-89 (an inhibitor of protein kinase A, 50 micromol/l). These results indicate the stimulatory influence of STZ on the action of hormone-sensitive lipase in isolated cells of white adipose tissue. The obtained outcomes suggest that in studies employing STZ, it is necessary to consider its direct effect upon lipolysis in adipocytes.
- MeSH
- Epinephrine pharmacology MeSH
- Hypoglycemic Agents pharmacology MeSH
- Enzyme Inhibitors pharmacology MeSH
- Insulin pharmacology MeSH
- Isoquinolines pharmacology MeSH
- Rats MeSH
- Lipolysis drug effects MeSH
- Rats, Wistar MeSH
- Antibiotics, Antineoplastic pharmacology MeSH
- Streptozocin pharmacology MeSH
- Sulfonamides * MeSH
- Sympathomimetics pharmacology MeSH
- In Vitro Techniques MeSH
- Adipocytes cytology drug effects metabolism MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine MeSH
- Hypoglycemic Agents MeSH
- Enzyme Inhibitors MeSH
- Insulin MeSH
- Isoquinolines MeSH
- N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide MeSH Browser
- Antibiotics, Antineoplastic MeSH
- Streptozocin MeSH
- Sulfonamides * MeSH
- Sympathomimetics MeSH
