The Sympathomimetic Actions of l-Ephedrine and d-Pseudoephedrine: Direct Receptor Activation or Norepinephrine Release?

Kobayashi, Shigeaki; Endou, Masayuki; Sakuraya, Fumika; Matsuda, Naoyuki; Zhang, Xiaohong; Azuma, Mitsue; Echigo, Noriyuki; Kemmotsu, Osamu; Hattori, Yuichi; Gando, Satoshi

doi:10.1213/01.ane.0000092917.96558.3c

Cited by 65 publications

(37 citation statements)

References 16 publications

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“…Ephedrine has been shown to bind to ␤1, ␤2, and ␤3 receptors expressed on Chinese hamster ovary cells (Vansal and Feller, 1999). It has been reported that despite evidence that ephedrine has direct effects in isolated tissues, the pressor response was shown to be indirectly mediated in vivo in the rat (Kobayashi et al, 2003). In contrast, the present results demonstrate that responses to ephedrine are directly mediated, whereas responses to amphetamine are dependent on an indirect mechanism.…”

Section: Downloaded Fromcontrasting

confidence: 82%

“…Other studies in isolated tissues have shown that ephedrine acts by direct stimulation of adrenergic receptors (Tye et al, 1967;Waldeck and Widmark, 1985;Bao et al, 1990;Kawasuji et al, 1996). It has recently been reported that despite evidence that ephedrine has direct effects in isolated tissues, the pressor response is completely indirectly mediated in vivo in the rat (Kobayashi et al, 2003).…”

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confidence: 97%

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Pressor Responses to Ephedrine Are Mediated by a Direct Mechanism in the Rat

Liles¹,

Dabisch²,

Hude³

et al. 2005

J Pharmacol Exp Ther

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The mechanism of the pressor response to ephedrine is controversial. In the present study. i.v. injections of ephedrine increased systemic and pulmonary arterial pressure, and i.a. injections decreased hindlimb blood flow in a dose-related manner. Responses to ephedrine were inhibited by ␣-receptor blocking agents and were not attenuated by blockade of the norepinephrine reuptake transporter (NET) or by catecholamine depletion using reserpine or a combination of reserpine and ␣-methyl-p-tyrosine, whereas responses to tyramine and amphetamine were inhibited by these treatments. The magnitude of the pressor response to ephedrine was similar in anesthetized and conscious rats. Tachyphylaxis developed to pressor responses to ephedrine and amphetamine with sequential injections; however, ephedrine tachyphylaxis differed in that subsequent responses to ␣-receptor agonists were attenuated. These results suggest that the systemic and pulmonary pressor and hindlimb vasoconstrictor responses to ephedrine are mediated by direct action on ␣-adrenergic receptors and that the release of norepinephrine from adrenergic terminals plays no significant role. These results provide support for the hypothesis that responses to ephedrine are directly mediated in the intact rat, whereas responses to amphetamine are mediated in a large part by the release of norepinephrine from adrenergic terminals.

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Section: Downloaded Fromcontrasting

confidence: 82%

mentioning

confidence: 97%

Pressor Responses to Ephedrine Are Mediated by a Direct Mechanism in the Rat

Liles¹,

Dabisch²,

Hude³

et al. 2005

J Pharmacol Exp Ther

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“…Pressure ( have been inconsistent (Kobayashi et al, 2003;Liles et al, 2006). Therefore, the present experiments were carried out in mice with targeted disruption of the Dbh gene that cannot synthesize noradrenaline (Thomas et al, 1995(Thomas et al, , 1997(Thomas et al, , 1998).…”

Section: Change In Mean Arterialmentioning

confidence: 99%

“…However, the mechanism of the pressor response to ephedrine is uncertain. Ephedrine has been thought to elicit a pressor response through the release of noradrenaline from adrenergic terminals (Fleckenstein and Burn, 1953;Burn and Rand, 1958;DeMoraes and Carvalho, 1968;Kobayashi et al, 2003). It has been reported that the pressor response to ephedrine is reduced following treatment with 6-hydroxydopamine to destroy adrenergic nerve terminals (Kobayashi et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Pressor responses to ephedrine are not impaired in dopamine β‐hydroxylase knockout mice

Liles

Baber

Deng

et al. 2007

British J Pharmacology

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Background and Purpose: Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model. Experimental Approach: Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine b-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh þ /-littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments. Key Results: In Dbh -/-mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh þ /-mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/-and Dbh þ /-mice. Conclusions and Implications:The present results in Dbh -/-mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh þ /-and Dbh -/-mice are useful for the study of direct and indirect mechanisms.

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“…Indeed, the aerial parts of different Ephedra species contain active alkaloids (Yeung, 1980), including the phenylpropylamino alkaloids ephedrine and pseudoephedrine. Ephedrine is a sympathomimetic agent (Astrup et al, 1995;Kobayashi et al, 2003) and its consumption may lead to increased cardiac rate and contractility as well as overstimulation of the central nervous system (Abourashed et al, 2003;Krizevski et al, 2012). However, E. foeminea species specifically lacks both ephedrine and pseudoephedrine (Abourashed et al, 2003;Krizevski et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Effect of Ephedra foeminea active compounds on cell viability and actin structures in cancer cell lines

Mendelovich¹,

Shoshan²,

Fridlender³

et al. 2017

J. Med. Plants Res.

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Ephedra is likely one of the oldest medicinal plants still currently in use. In folk medicine, extracts of Ephedra foeminea are commonly used to treat cancer patients. In relation to its traditional use, the aim of the present study was to determine the cytotoxic activity in vitro of E. foeminea extracts on cancer and non-cancer cells. Cell viability was determined using XTT assay, induction of apoptosis by cell sorting and caspase-3 inhibition, and the effects on cell cytoskeleton structure were detected using cell transfection utilizing different cytoskeleton markers. Chemical profiling, analysis of active extracts and identification of compounds was done using high pressure liquid chromatography (HPLC) and gas chromatography-mass spectroscopy (GCMS). E. foeminea leaf ethanol extract and E. foeminea fruit juice reduced cancer cell viability in vitro, whereas the water extract reduced cytotoxic activity in all cell lines. The extract's cytotoxic activity was conveyed at least partially via the induction of caspase 3-dependent cell apoptosis, and enhanced by the addition of Taxol. Both E. foeminea ethanol leaf extract and fruit juice affected actin-stained but not tubulin-stained filaments. Ethanol extract promoted the formation of invadopodia-like structures and fruit juice promoted the formation of large focal adhesion points in the treated cells. Active sub-fractions of E. foeminea extracts were found to contain several compounds including trans-sinapyl alcohol and trans-sinapaldehyde derivative.

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The Sympathomimetic Actions of l-Ephedrine and d-Pseudoephedrine: Direct Receptor Activation or Norepinephrine Release?

Abstract: The indirectly sympathomimetic property of l-ephedrine may be one of the mechanisms to explain why ephedrine is preferred over alpha-adrenergic agonists as a vasopressor for treatment of intraspinal anesthesia-induced hypotension in obstetrics.

Cited by 65 publications

References 16 publications

Pressor Responses to Ephedrine Are Mediated by a Direct Mechanism in the Rat

Pressor Responses to Ephedrine Are Mediated by a Direct Mechanism in the Rat

Pressor responses to ephedrine are not impaired in dopamine β‐hydroxylase knockout mice

Effect of Ephedra foeminea active compounds on cell viability and actin structures in cancer cell lines

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