Relationship between Configuration and Adrenergic β-Receptor Blocking Activity of Optical Isomers of 1-(4-Nitrophenyl)-2-isopropylaminoethanol (INPEA)

Almirante, L; Murmann, W

doi:10.1021/jm00323a002

Cited by 36 publications

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“…It is obvious that if a drug acts by way of only one of the isomers, the other is unnecessary. There are numerous papers pointing out differences between the R-and S-enantiomers and indicating that only the S-enantiomer is active in [3-blockade (e. g., [6,7] ).Carvedilol is a new racemic compound chemically designed to produce two complementary pharmacological effects: vasodilation and [3-blockade.The aim of our study was to investigate to what extent each of the two stereoisomers contribute to the pharmacological profile of carvedilol (Fig.l). Therefore, the [3-blocking, m-blocking and hypotensive activities of the stereoisomers and of the racemate were evaluated.…”

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confidence: 99%

Pharmacological characteristics of the stereoisomers of carvedilol

Bartsch¹,

Sponer²,

Strein³

et al. 1990

Eur J Clin Pharmacol

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The racemic compound carvedilol possesses two complementary pharmacological effects, vasodilation and beta-blockade. The R- and S-enantiomers of carvedilol and the racemate were investigated with respect to the beta-blocking, vasodilating, and hypotensive actions. In agreement with results obtained with other beta-blockers, only the S-enantiomer of carvedilol exerts beta-blocking effects. In contrast, no substantial difference between the enantiomers could be seen with respect to alpha-blockade. The greater hypotensive activity of S-carvedilol may be attributed to beta-blockade, which inhibits counter-regulatory mechanisms provoked by vasodilation. From these results it is concluded that there is a rationale for using carvedilol as the racemate. Using the S-enantiomer would lead to relatively strong beta-blockade with only a weak vasodilating effect. The R-enantiomer alone would act only as a hypotensive agent without beta-blockade.

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confidence: 99%

Pharmacological characteristics of the stereoisomers of carvedilol

Bartsch¹,

Sponer²,

Strein³

et al. 1990

Eur J Clin Pharmacol

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“…On the other hand, the protection afforded by practolol and the (-)-enantiomer of sotalol (MJ1999)-drugs which lack membranestabilizing properties (Singh & Vaughan Williams, 1970)-suggests that /3-adrenoceptor blockade alone can be responsible for this effect; the (+Ienantiomer of sotalol, which is weak in this respect (Patil, 1968) proved inactive against ouabain. Similarly, the (-)-enantiomer of INPEA, which is also weak in membrane-stabilizing properties (Singh & Vaughan Williams, 1971), but is responsible for all the /3-adrenoceptor blocking activity of this compound (Patil, 1968;Almirante & Murmann, 1966) showed protective activity against ouabain toxicity, though of a low order, such that activity could not be established for (&)-INPEA below toxic doses. cr-Methyl INPEA, which is only very weakly active on cardiac P-adrenoceptors (Somani, 1969), also showed only slight activity in this situation.…”

Section: Discussionmentioning

confidence: 99%

The activity of β-adrenoceptor blocking agents in protecting mice from the cardiotoxic effects of ouabain

Lavender

Parkes

1973

Journal of Pharmacy and Pharmacology

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A method is described for the assessment of the protective activity of drugs against the lethal effect of intravenously infused ouabain in mice. Electrocardiographic studies confirmed that protection is exerted against a cardiotoxic action of the glycoside. Activities are quoted for some β‐adrenoceptor blocking agents. Both (‐)‐ and (+)‐enantiomers of propranolol were active but only the (‐)‐enantiomer of sotalol and INPEA‐drugs devoid of membrane‐stabilizing properties.

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“…The drugs studied were diphenylhydantoin, trimethadione, and the adrenergic agents propranolol [l-isopropylamin0-3-(l-naphthyloxy)-2-propanol hydrochloride], pronethalol [~,L-l-(2'-naphthyl)-2-isopropylaminoethanol hydrochloride], D ( -)-and L( +)-INPEA [D( -)-and ~(+)-1-(4'-nitropheny1)-2-isopropylaminoethanol hydrochloride], and MJ1999 [4'-(2-isopropylamino-lhydroxyethyl)methanesulfonanilide]. Except for L ( +)-INPEA, all these compounds are well-established peripheral 0-adrenergic blocking agents (12).…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Evaluation of Seizures Induced by Electrical Stimulation of the Hippocampus

Yeoh

Wolf

1970

Journal of Pharmaceutical Sciences

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0 A method to induce minimal seizures in unrestrained rats uia bipolar electrodes implanted in the right dorsal hippocampus has been described. The threshold for such seizures is reproducible, stable over time, and elevated by trimethadione and high doses of diphenylhydantoin. Propranolol and pronethalol also raise seizure threshold, but MJ1999 and D(-)-and L(+)-INPEA are ineffective. The adrenergic agents do not seem to alter seizure threshold by their ability to block preceptors. Keyphrases 0 Hippocampal stimulation-bipolar electrodes 0 Convulsive seizures-electrical stimulation, hippocampus 0 Electrically produced seizures-convulsive threshold 0 Anticonvulsants effect-electrically produced seizures

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Relationship between Configuration and Adrenergic β-Receptor Blocking Activity of Optical Isomers of 1-(4-Nitrophenyl)-2-isopropylaminoethanol (INPEA)

Cited by 36 publications

References 0 publications

Pharmacological characteristics of the stereoisomers of carvedilol

Pharmacological characteristics of the stereoisomers of carvedilol

The activity of β-adrenoceptor blocking agents in protecting mice from the cardiotoxic effects of ouabain

Pharmacological Evaluation of Seizures Induced by Electrical Stimulation of the Hippocampus

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