Efficacy of a mephentermine-based product as a vasopressor and a cardiac performance enhancer when given intramuscularly to cattle.

The goal of this study was to confirm the vasopressor and cardiac effects of POTENAY® INJETÁVEL (POT), a mephentermine-based product, given to cattle with induced vascular/cardiac depression. Ten healthy Holstein cattle (206 ± 13 kg) followed a randomized-complete-block design (RCBD) utilizing crossover study design. Each animal randomly received (1 ml/25 kg, IM) of either POT (n = 10) or volume-matched placebo control (0.9%NaCl, CP, n = 10). A subset of animals (n = 5) received POT first (day 0) while the remaining (n = 5) received CP; after a six-day washout period, cattle received the opposite compound. Animals were anesthetized and catheterized for systemic/left ventricular hemodynamic monitoring. Myocardial dysfunction/hypotension was induced by increasing the end-tidal isoflurane concentration until arterial blood pressure was 20% lower than at baseline and remained stable. Once the animal was determined to be hypotensive and hemodynamically stable, steady-state hypotensive baseline data (BL2) were acquired, and treatment with either POT or CP was given. Data were acquired post-treatment at every 15 min for 90 min. POT improved cardiac output (+68 L/min, ±14%, p < 0.05), MAP (+14 mmHg, ±4%, p < 0.05), HR (+22 bpm, ±8%, p < 0.05), and peak rates of ventricular pressure change during both systole (dP/dtmax : +37 mmHg/s ±13%, p < 0.05) and diastole (dP/dtmin : +31 mmHg/s, ±7%, p < 0.05). No improvements were noted following placebo-control administration. Results indicate that POT improves cardiac performance and systemic hemodynamics in cattle with induced cardiovascular depression when given as single intramuscular injection.

Comparison of bolus phenylephrine, ephedrine and mephentermine for maintenance of arterial pressure during spinal anesthesia in cesarean section.

INTRODUCTION: Hypotension is common following spinal anesthesia. Various vasopressors have been indicated to prevent it. The study compares three such agents namely phenylephrine, ephedrine and mephentermine. METHODS: The study included 90 patients undergoing elective and emergency cesarean section who developed hypotension following subarachnoid blockade. Parturient were randomly divided into three groups each group had 30 patients. Group P received bolus of Phenylephrine 25 microgram, where as group E received Ephedrine 5mg and Group M received Mephentermine 6mg. RESULTS: It was found that rise of blood pressure was significantly higher in case of phenylephrine group in first six minutes, after the bolus, there was significant reduction in the heart rate in phenylephrine group, but there was tachycardia following administration of bolus ephedrine and mephenteramine. Neonatal APGAR score were similar in all three groups. CONCLUSIONS: All three drugs maintained hemodynamics within 20 percent of the baseline values on intravenous administration.

Mephentermine dependence without psychosis: a Brazilian case report.

BACKGROUND: Substance abuse is a serious health concern. This report presents the case of a 22-year-old Brazilian man with a history of mephentermine use who fulfils all the criteria for chemical dependence listed by ICD-10. Mephentermine is a sympathomimetic agent derived from methamphetamine which, in Brazil, is restricted to veterinary use. CASE DESCRIPTION: The subject used the substance at a high dose (120 mg) to improve his physical performance while working out at a gym. His symptoms included anorexia and insomnia. After days of intense activity, he felt fatigue and soreness. A physical examination revealed scars on both forearms from the injections and a psychological examination revealed moderate speech and motor agitation. CONCLUSIONS: Cases such as this may be common among the general public. They should have some bearing upon medical practice and public health policies involving drugs.

The effect of vasopressor agents upon uterine artery blood flow velocity in the gravid guinea pig subjected to ritodrine infusion.

The purpose of the present study was to assess the effects of intravenously administered vasopressors upon uterine artery blood flow velocity (UBFV) in the gravid guinea pig subjected to ritodrine infusion. Fourteen experiments were performed in 14 chronically instrumented pregnant guinea pigs near term. Immediately following a 1-h intravenous infusion of ritodrine (0.05-0.20 mg.kg.min-1), each animal received an intravenous bolus of vasopressor solution: 1) epinephrine, 0.001 mg/kg; 2) phenylephrine, 0.01 mg/kg; 3) mephentermine, 1.0 mg/kg; 4) ephedrine, 1.0 mg/kg; or 5) placebo. The experimental sequence was performed five times, so that each animal received all five solutions. The vasopressor sequence was randomly altered between animals. Infusion of ritodrine increased maternal heart rate 18 +/- 1% (P less than .0001), decreased maternal mean arterial pressure (MMAP) 4 +/- 1% (P less than .01), and decreased UBFV 5 +/- 1% (P less than .001). The four active vasopressor solutions resulted in similar, though not equivalent, increases in MMAP. Further, the MMAP response to each active vasopressor differed from the response to placebo (P less than .0001). Epinephrine and phenylephrine each significantly decreased UBFV (P less than .002). Ephedrine clearly preserved UBFV, whereas mephentermine appeared to result in an intermediate response.

Present state of alpha- and beta-adrenergic drugs I. The adrenergic receptor.

The cardiovascular alpha adrenergic receptors evoke vasoconstriction, the cardiovascular beta receptors evoke vasodilation and cardiac stimulation. All blood vessels have both alpha and beta receptors. In some areas, for example skin and kidney, the alpha receptors predominate. In some vascular beds, for example the nutrient vessels in skeletal muscle, beta receptors predominate. In other beds, such as coronary, visceral, and connective tissue both receptors are active. The cardiovascular effects of adrenergic agonists depend on which receptor they act on. Phenylephrine is specific for alpha receptors. Isoproterenol is specific for beta receptors. Epinephrine and norepinephrine act on both. The real value of knowing the receptor specificity of each agonist is that side effects can more easily be predicted. For example, adrenergic cardiac stimulants are antiasthmatics. Therefore, adrenergic antiasthmatics can produce excessive cardiac stimulation. For the future, agonists that are not only receptor-specific but also tissue-specific will be developed. The first of these in the United States is terbutaline. The rest of the world has in addition a similar drug, salbutamol. No one knows if this drug will be approved for use by American physicians.

Effects of verapamil on myocardial contractility, cardiac adenosine 3,'5'-monophosphate and heart phosphorylase.

The effects of verapamil on myocardial isometric force on contraction, cardiac adenosine 3,'5'-monophosphate (cyclic AMP) and heart phosphorylase alpha activity were studied in the isolated perfused rat heart. When hearts were perfused with verapamil (5.98 times 10- minus 8 M), force of contraction was reduced approximately 50% within 4 to 5 minutes; at this point, the concentration of cyclic AMP was significantly lower than control but phosphorylase alpha activity was unchanged. In hearts perfused continuously for 60 minutes with verapamil, force of contraction and cyclic AMP levels returned to normal within 20 minutes after administration of verapamil was begun. Isoproterenol (0.355 nmol/min) reversed the depressant effect of verapamil on cardiac contractility and restored heart cyclic AMP levels to normal. Methoxamine (35.5 nmol/min) given to verapamil-depressed hearts, caused contractile force to return to normal, but cardiac cyclic AMP levels remained low. Mephentermine (23.0 nmol/min) had no effect on cardiac contraction, cyclic AMP or phosphorylase alpha activity in hearts depressed by verapamil. It was concluded that with the concentration of verapamil used in these experiments, the drug caused a transient decrease in force of contraction and myocardial cyclic AMP. Both the depression in myocardial contractility and in cardiac cyclic AMP caused by verapamil were reversed promptly by isoproterenol, whereas methoxamine overcame acutely only the negative inotropic effect of verapamil. Mephentermine had no effect on hearts depressed by verapamil.

The effect of seven vasopressors of halothane MAC in dogs.

We evaluated the effects of ephedrine, mephentermine, metaraminol, phenylephrine, methoxamine, noradrenaline and adrenaline on halothane anaesthetic requirement (MAC) in dogs. MAC increased significantly only during ephedrine infusion (50%) although significance was approached with mephentermine (21%). Phenylephrine, metaraminol, methoxamine, noradrenaline and adrenaline did not change MAC. Arterial pressure was increased 50-100% with all agents. Our results support the hypothesis that anaesthetic requirement may be related, in part, to release of brain noradrenaline.

[Clinical-pharmacological studies on the effect of mephentermin and methamphetamine on the hemodynamics of the lung circulation]. / Klinisch-pharmakologische Untersuchungen zur Wirkung von Mephentermin und Methamphetamin auf die Hämodynamik der Lungenstrombahn

In haemodynamic investigations of altogether 40 male probands with normal and restricted functional capacity of the lungs the result of an intravenous injection of mephentermine (30 mg) or methamphetamine (15 mg) was a transient increase of the mean pressure in the pulmonary artery and of the resistance of the pulmonary vessels. Temporarily parallel the arterial mean pressure and the resistance of the vessels in the greater circulatory system in most cases increased by about the same, in healthy persons after application of methamphetamine by a smaller relative amount. In the dosage used the vasoconstrictive effect of methamphetamine was altogether only somewhat more expressed. At the time of the maximum increase of the mean pressure of the pulmonary artery in healthy persons methamphetamine had a negative chronotropic and inotropic effect. It is referred to practical therapeutic consequences.

Metabolic and inotropic effects of verapamil in perfused rat heart.

The effect of verapamil on myocardial contractility, heart adenosine 3', 5'-monophosphate (cyclic AMP) and cardiac phosphorylase a activity was studied in isolated perfused rat hearts. In a concentration of 0.025 mug/ml, verapamil decreased force of contraction 50% and caused a significant fall in heart cyclic AMP within 4 to 5 min after perfusion with the drug was begun. When perfusion of the heart with medium containing verapamil was continued for 60 min, contractile force gradually returned to control. at the end of 60 min of perfusion with verapamil, the myocardial concentration of cyclic AMP was not different from that measured in hearts perfused with contro medium for a similar time period. Isoproterenol, given at the point of maximal contractile depression induced by verapamil, restored normal force of contraction and raised cardiac cyclic AMP to the same level as that observed when the catecholamine was given to untreated hearts; When methoxamine was administered to hearts depressed by verapamil, contractility returned to normal, but cyclic AMP content remained below control values.

Differential effects of the optical isomers of amphetamine on neuronal activity in the reticular formation and caudate nucleus of the rat.

The activity of neurons in the caudate nucleus and reticular formation was recorded following intraperitoneal injection of the optical isomers of amphetamine. In general, D-amphetamine sulfate (2.0 mg/kg) produced an initial increase in firing rate of neurons in the caudate nucleus approximately 8-10 min following intraperitoneal injection, and a subsequent depression of firing rat which lasted for a period of time of from 70 to 120 min. Similar injections of L-amphetamine sulfate produced only a depression of activity in the caudate nucleus which was less marked and of lesser duration. Mephentermine sulfate (6.0 mg/kg), a peripheral sympathomimetic, did not produce these effects. Both D-amphetamine and L-amphetamine sulfate at the same dose produced an increase in firing rate of neurons in the reticular formation, although that produced by the L-isomer was less marked and of lesser duration. Mephentermine sulfate also produced an increase in reticular formation neuronal activity comparable to that produced by L-amphetamine sulfate. In some cases, neuronal activity was held for prolonged periods of time following injection. In the caudate nucleus, a rebound increase in firing rate was observed following the marked depression produced by both isomers of amphetamine. A rebound depression of activity was observed in the reticular formation following the initial increase in neuronal activity produced by these drugs. The results are discussed in terms of the known biochemical and behavioral effects of the stereoisomers of amphetamine.