Cardiovascular Effects of 2-(O-Chlorophenyl)-2-Methylaminocyclohexanone (Ci-581) in Rats

Abstract

2-(0-chlorophenyl)-2-methylaminocyclohexanone (CI-581), a derivative of phencyclidine, was shown to depress the cardiovascular system in conscious rats and in rats anaesthetized with pentobarbitone and urethane. In pithed animals, however, there was a substantial rise in blood pressure, suggesting that CI-581 may act on the central cardiovascular regulatory mechanisms. The pressor response to CI-581 in pithed animals was considerably reduced by phenoxybenzamine and phentolamine. In reserpinized animals, the pressor response to CI-581 was abolished but could be restored by infusions with noradrenaline. Thus, CI-581 may act indirectly by releasing catecholamines from peripheral stores. In adrenalectomized rats, the increase in blood pressure elicited by CI-581 was abolished by pre-treatment with reserpine. The data indicate that the peripheral release of catecholamines by CI-581 may be derived from more than one storage site.

Effects of Ketamine on Vascular Smooth Muscle Function

“…The plasma levels (e.g., 6 x 10'to 2 x 10' M; Cohen, Chan, Way & Trevor, 1973) of anaesthetic doses of ketamine (20 to 40 mg/kg), after its intravenous injection into rats, are highest within the first few minutes. During this time, there is usually a short-lived vasodepressor response (Chang et al, 1969). Since the potent, fast-acting (as well as easily reversible) inhibitory effects observed here with ketamine take place with similar concentrations of the amine-anaesthetic, it seems reasonable to suggest that the initial fall in blood pressure, at least in the rat, is due, at least in part, to a direct action of ketamine on vascular smooth muscle.…”

“…Among other side-effects (Dundee & Wyant, 1974;Hamilton, 1976), ketamine has been shown to produce marked rises in blood pressure, cardiac output, heart rate and peripheral blood flow in man and some other mammals, including the rat (Corsen & Domino, 1966;Virtue, Alanis, Mari, Lafargue, Vogel & Metcalf, 1967;Traber, Wilson & Priano, 1968;Chang, Chan & Ganendran, 1969;Dundee & Wyant, 1974;Hug, 1979).…”

Effects of Ketamine on Vascular Smooth Muscle Function

“…During this time, there is usually a short-lived vasodepressor response (Chang et al, 1969). Since the potent, fast-acting (as well as easily reversible) inhibitory effects observed here with ketamine take place with similar concentrations of the amine-anaesthetic, it seems reasonable to suggest that the initial fall in blood pressure, at least in the rat, is due, at least in part, to a direct action of ketamine on vascular smooth muscle.…”

“…Since the potent, fast-acting (as well as easily reversible) inhibitory effects observed here with ketamine take place with similar concentrations of the amine-anaesthetic, it seems reasonable to suggest that the initial fall in blood pressure, at least in the rat, is due, at least in part, to a direct action of ketamine on vascular smooth muscle. Although it has been suggested by several workers that either actions on the sympathetic nervous system (Chang et al, 1969;Traber & Wilson, 1969) or a cocaine-like action of ketamine on vascular muscle (Montel, Starke, Gorlitz & Schumann, 1973;Nedergaard, 1973) may account for its pressor activity in several mammalian species, recent experiments by and Clanachan, McGrath & MacKenzie (1976), using pithed rats, a-adrenoceptor blocking agents, depletion of tissue noradrenaline and adrenalectomy would seem to eliminate mediation by either liberation of catecholamines or action on adrenergic vascular neuroeffectors, at least for the rat. Our results demonstrating a unique, and specific, potentiation by ketamine of 5-HT-induced contractile responses could, however, explain the secondary peripherally-mediated pressor response observed in the rat, after ketamine administration and possibly for other mammals as well.…”

“…Among other side-effects (Dundee & Wyant, 1974;Hamilton, 1976), ketamine has been shown to produce marked rises in blood pressure, cardiac output, heart rate and peripheral blood flow in man and some other mammals, including the rat (Corsen & Domino, 1966;Virtue, Alanis, Mari, Lafargue, Vogel & Metcalf, 1967;Traber, Wilson & Priano, 1968;Chang, Chan & Ganendran, 1969; Dundee & Wyant, 1974;Hug, 1979).…”