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Try out PMC Labs and tell us what you think. Learn More. MDEA produced a transient but nonificant fall in diastolic pressure. The pressor response produced by MDA was accompanied by bradycardia. Substance abuse is widespread, especially in the young adult population, and is associated with numerous complications see Ghuran et al. Ingestion of amphetamine derivatives has been associated with acute adverse reactions such as hyperthermia, hypertension, tachycardia, acute myocardial infarction and increased motor activities such as jaw clenching Hegadoren et al.
Consistent with clinical s, animal studies have also shown increases in blood pressure, disruption in thermoregulation, inhibition of the jaw opening reflex and increased locomotor activity Gold et al. Although much of the research into the actions of amphetamine derivatives has focused on serotonergic and dopaminergic systems, there is evidence also for the involvement of the noradrenergic system, particularly in the periphery. Users of methylenedioxymethamphetamine MDMA are reported to have elevated plasma catecholamine levels, which may be due to noradrenergic hyperactivity and may be linked to cardiovascular complications Stuerenburg et al.
A cannula was inserted into the abdominal aorta below the renal arteries and fixed into place with tissue adhesive. The implant was then sutured to the abdominal wall. The abdominal wall and skin incision were closed with silk suturing. Motion and temperature sensors built into the device measured locomotor activity and core body temperature.
Postoperative analgesia was not given. Animals were allowed to recover for at least 7 days before experiments were performed. On experimental days, a PhysiolTel-Receiver model RPC-1 was placed under each individual animal cage, enabling recording of the various parameters.
All recordings were obtained at room temperature Following overdose of CO 2 and exsanguination, thoracic aorta or whole vas deferens was removed from untreated rats and placed in Krebs—Henseleit solution of the following composition m M : NaCl ; NaHCO 3 25; D -glucose A second concentration—response curve to noradrenaline in the continuing presence of MDEA or vehicle was carried out.
The shift in noradrenaline potency produced by MDEA was corrected for the shift in noradrenaline potency, which occurred in a paired vehicle experiment.
Epididymal portions of rat vas deferens were obtained. Agonists or vehicle were added cumulatively in 0. Pellets were reconstituted in five volumes submandibular10 volumes kidney, vas deferens or 25 volumes Sf9 cells of incubation buffer. Radioactivity retained on filters was determined by liquid scintillation spectroscopy. Area under the curve for heart rate, systolic and diastolic pressure, core body temperature and locomotor activity were calculated from the preinjection baseline using the trapezoidal method.
All data were analysed and compared with the effects of vehicle using one-way ANOVA with Bonferroni multiple comparison test. Systolic, diastolic and mean blood pressures were recorded, but except where changes in systolic or diastolic differed, mean blood pressure is discussed. Table 1. Figure 1a shows the effect of different amphetamine derivatives on mean blood pressure. Baseline mean arterial pressure, heart rate, core body temperature and locomotor activity in rats prior to treatment with vehicle, amphetamine derivatives or BRL BRL.
For clarity, experiments with BRL are omitted from Figure 1. Baseline values were similar between all treatment groups when compared to the vehicle group Table 1. MDMA did not have a ificant effect on heart rate. MDA elicited an initial ificant bradycardia, and MDEA elicited a late tachycardia, which reached ificance as compared to the effects of vehicle Figure 1b. MDA produced a biphasic response consisting of an initial hypothermia followed by hyperthermia.
When given alone, only MDA produced a ificant increase in locomotor activity as compared to the effects of vehicle Figure 3Table 3. Each group consisted of five to seven rats. Each group consisted of four to five rats. Under these conditions, the twitch to a single stimulus was 0. Each group consisted of four to eight rats. MDMA data are taken from Lavelle et al. The p K i values obtained are shown in Table 4. In human studies of MDMA, doses ranging between 1. These are consistent with human studies that have also shown increases in arterial pressure with the above compounds Gouzoulis et al.
MDEA had no ificant effect on systolic pressure but transiently admittedly, nonificantly reduced diastolic pressure. Hence, the pressor responses elicited by the amphetamine derivatives can be attributed to direct and indirect sympathomimetic actions in the periphery, and in both cases MDEA should be less active. The major effect seen on heart rate in conscious rats was that MDA elicited an initial bradycardia. All three agents tended to increase heart rate later, but this reached ificance only for MDEA.
These changes may be, at least, partly baroreflex responses to changes in blood pressure, given that MDA produced the largest increase in blood pressure and MDEA produced a fall. In conscious animals and humans, MDMA has been shown to produce no change in heart rate, bradycardia at high doses or tachycardia O'Cain et al. The discrepancies seen in the literature may be due to the different recording procedures, ambient temperature and species or strains used.
The mechanisms of the hypothermic and hyperthermic responses produced by the amphetamine derivatives are still not clear. The serotonergic, noradrenergic and dopaminergic neurotransmitter systems have all been implicated in the mediation of hypothermia. D -fenfluramine has been shown to induce both 5-HT and dopamine release and increase extracellular 5-HT and dopamine levels in the brain.
The increase in extracellular dopamine concentration involves 5-HT receptors in addition to action at dopamine uptake sites Cryan et al. As with the hypothermic response, the mechanisms involved in producing a hyperthermic response are also unclear.
It has been suggested that a central dopamine and 5-HT interaction is involved and that 5-HT 2A and dopamine D 1 receptors are involved in the mediation of hyperthermia Sugimoto et al. In the present study, MDMA did not produce hyperthermia. All three amphetamine derivatives tended to cause an increase in locomotor activity, but this reached ificance only for MDA. One of the major findings of this study is that MDA has overall more marked cardiovascular, temperature and locomotor actions than the other agents examined.
Plasma half-lives of around 2. This study was supported by the Health Research Board Ireland. National Center for Biotechnology InformationU. Journal List Br J Pharmacol v. Br J Pharmacol. Published online Feb Author information Article notes Copyright and information Disclaimer.
CopyrightNature Publishing Group. This article has been cited by other articles in PMC. Introduction Substance abuse is widespread, especially in the young adult population, and is associated with numerous complications see Ghuran et al. Rat aorta and vas deferens Following overdose of CO 2 and exsanguination, thoracic aorta or whole vas deferens was removed from untreated rats and placed in Krebs—Henseleit solution of the following composition m M : NaCl ; NaHCO 3 25; D -glucose Rat vas deferens: nerve-mediated contractions Epididymal portions of rat vas deferens were obtained.
Drugs were dissolved in distilled water.
Cardiovascular responses to MDMA analogues in conscious rats Mean blood pressure Systolic, diastolic and mean blood pressures were recorded, but except where changes in systolic or diastolic differed, mean blood pressure is discussed. Open in a separate window. Figure 1. Table 1 Baseline mean arterial pressure, heart rate, core body temperature and locomotor activity in rats prior to treatment with vehicle, amphetamine derivatives or BRL BRL. Heart rate Baseline values were similar between all treatment groups when compared to the vehicle group Table 1.
Figure 2. Figure 3.
Figure 4. Figure 5. Figure 6. Locomotor activity All three amphetamine derivatives tended to cause an increase in locomotor activity, but this reached ificance only for MDA. Actions of MDA One of the major findings of this study is that MDA has overall more marked cardiovascular, temperature and locomotor actions than the other agents examined.
Effects of methylenedioxymethamphetamine on noradrenaline-evoked contractions of rat right ventricle and small mesenteric artery. Changes in the cardiovascular responsiveness and cardiotoxicity elicited during binge administration of ecstasy. An evaluation of cytochrome P isoform activities in the female dark agouti DA rat: relevance to its use as a model of the CYP2D6 poor metaboliser phenotype. A novel neurotensin analog blocks cocaine- and D -amphetamine-induced hyperactivity.
Relationship between the inhibition constant K i and the concentration of inhibitor which causes 50 per cent inhibition IC 50 of an enzymatic reaction. Effects of amphetamine derivatives and cathinone on noradrenaline-evoked contractions of rat right ventricle.
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