Positive inotropic action of .KAPPA. opiate agonists, ethylketocyclazocine and dynorphin-A(1-13), in isolated rat atrium.

Maeda, Shin; Nakamae, Junji; Inoki, Reizo

doi:10.1254/jjp.45.125

Cited by 4 publications

(2 citation statements)

References 11 publications

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“…Gautret and Schmitt (1985) showed that dynorphin produced bradycardia in pentobarbital-anesthetized rats, even following bilateral vagotomy, suggesting a direct action on the heart. Further support for a direct inhibitory action of kappa agonists on the heart comes from a study by Maeda et al (1987), who showed a decrease in beat frequency in the isolated rat atrium following treatment with EKC and dynorphin. In this study, the kappa agonists did produce a positive inotropic effect, indicating that kappa agonists can have some excitatory effects in the periphery.…”

Section: Discussionmentioning

confidence: 99%

“…With any pharmacological treatment for drug abuse, it is inevitable that the treatment drug and the abused drug will be used in combination in some individuals that relapse to drug use. While a number of studies have looked at the effects of kappa agonists on cardiovascular function, most of these studies have been performed in isolated organ preparations (e.g., Kannan and Seip, 1986;Maeda et al, 1987;Wong et al, 1990) or anesthetized animals (Laurent and Schmitt, 1983;Punnen and Sapru, 1986;Rochford et al, 1991). The purpose of this study was to determine the cardiovascular effects of two representative kappa opioid agonists in a conscious, non-human primate model of cardiovascular function.…”

Section: Introductionmentioning

confidence: 99%

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Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys

Schindler¹,

Graczyk²,

Gilman³

et al. 2007

European Journal of Pharmacology

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As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((±)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

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Section: Discussionmentioning

confidence: 99%