Pharmacological properties of the enantiomers of idazoxan: possible separation between their alpha-adrenoceptor blocking effects.

The alpha-adrenoceptor blocking properties of the two enantiomers of idazoxan have been investigated in rats, dogs and chicks, as well as their agonistic effects in pithed rats. At peripheral sites, (+) idazoxan was equipotent for blocking both postsynaptic alpha-1 and alpha-2 adrenoceptors of the rat and revealed to be a potent antagonist at presynaptic sites of rats and dogs. (-) Idazoxan revealed to be selective for postsynaptic alpha-2 adrenoceptors with an apparent selectivity ratio of about 10.

Antagonistic effects of S9871 or (imidazolinyl-2)-2-dihydro 2,3 benzofurane and its stereoisomers on some central and peripheral actions of alpha 2-agonists.

(+/-) and (+), but not (-) S9871 are new alpha 2-adrenoceptor selective antagonists. The effect of the racemic mixture and of the stereoisomers on cardiovascular and sedative responses to clonidine have been studied in rats and chickens, respectively. Blockade of central alpha 2-adrenoceptors was also measured as a recovery of the sympathoinhibitory effect induced by intravenous administration of B-HT 933 (azepexole).

Stereoselectivity of central alpha-adrenoceptors involved in sleep induced by clonidine in chickens.

The stereoselectivity of central alpha 2-adrenoceptors involved in sleep induced in chicks by clonidine, suggested by the results observed with the stereoisomers of idazoxan, was further investigated with the stereoisomers of (imidazolinyl-2)-2-dihydro-2,3-benzofurane (S9871) and those of (imidazolinyl-2)-2-benzocyclobutane (S10089). As for the stereoisomers of idazoxan, there was not a good separation between the effects of the stereoisomers of S10089. In contrast, there was a clearcut separation between the effects of (+)S9871 (antagonist) and (-)S9871 (no effect against the action of clonidine).

[In vivo and in vitro study of (N-piperidinomethyl)-2-chromanne on pre- and postsynaptic alpha-adrenoreceptors in the rat].

The alpha-adrenoceptors blocking effect of (N-piperidinomethyl)-2-chromanne was studied in vivo and in vitro in the rat. In the pithed rat, (N-piperidinomethyl)-2-chromanne (1 mg/kg i.v.

[Partial agonist properties of a new derivative of dihydrobenzofuran, S 9871, and its stereoisomers in pithed rats].

In the pithed rat, (imidazolinyl-2)-2 dihydro 2,3 benzofuran or S 9871 and its stereoisomers were found to block alpha-adrenoceptors. In the present investigation the agonistic effect were studied in pithed rats. With (+/-) and (+) S 9871 this effect is compatible with a stimulation of alpha 1-adrenoceptors and the effect of (-) stereoisomer with a stimulation of alpha 1 and alpha 2 adrenoceptors.

(Imidazolinyl-2)-2-benzodioxane 1-4 (idazoxan) and its stereoisomers, new alpha 2-antagonists.

Since (+/-) idazoxan is well known as alpha 2-antagonist, the present report described some results on the alpha-adrenoceptor blocking properties of the stereoisomers of idazoxan. At peripheral sites, (+) idazoxan revealed to be equipotent for blocking postsynaptic alpha 1- and alpha 2-adrenoceptors of the rat. On the other hand, it revealed to be a full antagonist of the inhibitory effects of clonidine on presynaptic alpha 2-adrenoceptors of rats.

Pre- and postsynaptic alpha-adrenoceptor blocking properties of a new dihydrobenzofurane derivative (imidazolinyl-2)-2-dihydro 2,3 benzofurane (S 9871) and its stereoisomers in rats.

In the present investigation, the alpha-adrenoceptor blocking effect of (imidazolinyl-2)-2-dihydro 2,3 benzofurane or S 9871 and its stereoisomers was studied. In the pithed rat (+/-) and (+) S 9871 competitively antagonized the pressor effects of azepexole and clonidine more effectively than those of cirazoline and phenylephrine. (-) S 9871 only blocked the pressor response of the alpha 1-agonists used: phenylephrine and cirazoline.

[Nature of alpha receptors implicated in the hypertensive effect of high doses of isoprenaline in dogs and rats].

Isoproterenol injected intravenously in dogs (3 mg/kg-1) and rats (5 mg/kg-1) induced an increase in blood pressure. After alpha 1 blockade (by AR-C 239, 0.1 mg .

Peripheral postsynaptic alpha-adrenoceptor blocking properties of some new dihydrobenzofurane and imidazoline derivatives in pithed rats.

Peripheral postsynaptic alpha-adrenoceptor blocking properties of six new dihydrobenzofurane and imidazoline derivatives have been investigated in pithed rat against the pressor effects of phenylephrine and cirazoline (alpha 1-agonists) and clonidine and azepexole (alpha 2-agonists). Except for (N-methylimidazolinyl-2)-2 dihydro-2,3 benzofurane (II) that acted neither on alpha 1- nor alpha 2-adrenoceptors, all the compounds revealed blocking effects - plus or minor - on both alpha 1- and alpha 2-adrenoceptors. (Imidazolinyl-2)-2-chloro-7 dihydro-2,3-benzofurane (IV) is equipotent in blocking both alpha 1- and alpha 2-adrenoceptors.

[Effect of 2 new derivatives of imidazoline and their optical isomers on postsynaptic alpha adrenergic receptors in pithed rats].

The effects of the stereoisomers of two alpha adrenoceptor antagonists [S 10089 (Imidazolinyl-2)-2 benzocyclobutane and S 9871 (Imidazolinyl-2)-2 dihydro 2,3 benzofuran] were studied in pithed Rats. Vasoconstriction elicited via stimulation of alpha 1 adrenoceptors by cirazoline was antagonized, stimulation of alpha 2 adrenoceptors by azepexole was also antagonized by all these derivatives except (-) S 9871 which was ineffective on the pressor response of azepexole.

[Interactions between alpha 1, alpha 2 and beta receptors in the blood pressure effects of adrenaline and noradrenaline in the dog].

In anaesthetized dog, the adrenaline induced hypertension is reversed by both alpha 1- and alpha 2-adrenoceptor blocking agents such as AR-C 239 and yohimbine. After alpha 1 or alpha 2 and beta-blockade, adrenaline induced again an increase in blood pressure. This hypertensive effect was suppressed by an alpha 2-adrenoceptor blocking agent when an alpha 1-adrenoceptor blocking was responsible for the reversal of adrenaline-induced hypertension, and conversely.

Action of stereoisomers of (imidazolinyl-2)-2-benzodioxane-1-4 or 2-(2-(1,4-benzodioxanyl))-2-imidazoline (170 150; RX 781094) on peripheral presynaptic and central alpha 2-adrenoceptors.

In the vas deferens of the rat, (-)-170 150 (imidazolinyl-2)-benzodioxane-1-4 or 2-(2-(1,4-benzodioxanyl))-2-imidazoline appeared to be more selective than (+)-170 150 for antagonizing the inhibitory effects of clonidine on the twitch response. In contrast, (+)-170 150 was the most potent of the two isomers for antagonizing the centrally mediated clonidine- or azepexole-induced sleep in chickens. These unexpected results seem to indicate that there are several subpopulations of alpha 2-adrenoceptors.

In vitro studies with (imidazolinyl-2)-2-benzodioxane-1-4 ((+/-)-170 150), a new potent alpha 2-adrenoceptor blocking agent.

In rat vas deferens, (+/-)-170 150 proved to be an alpha 2-adrenoceptor blocking agent with a high alpha 2/alpha 1 selectivity ratio. In rat cerebrocortical membranes, (+/-)-170 150 was seven times more potent than yohimbine for inhibiting specific [3H]clonidine binding. However, (+/-)-170 150 appeared to be 3.

[Comparative study of piperoxan and 2-(2-imidazolinyl)-1, 4-benzodioxane (170 150) on pre- and postsynaptic receptors in the rat].

1. 170 150 (imidazolinyl-2)-2-benzodioxane 1-4), as does piperoxan, competitively antagonizes the hypertension induced by clonidine in the pithed rat. Piperoxan appears slightly less potent than 170 150 in this preparation as shown by the comparison of the apparent pA10 values: 5.

Interaction between mianserin and clonidine at alpha 2-adrenoceptors.

The purpose of the present study was to characterize the effects of mianserin at alpha 2-adrenoceptors. Firstly, the action of mianserin on postganglionic sympathetic fibres has been studied using the tachycardia induced by stimulation of the cardiac nerve in dogs. Mianserin increased this tachycardia, but could not prevent the inhibitory effect of clonidine in this model.

Pre- and postsynaptic a-adrenoceptor blockade by (imidazolinyl-2)-2-benzodioxane 1-4 (170 150): antagonistic action on the central effects of clonidine.

While the specificities of alpha 1-adrenoceptor blocking agents are considered as satisfactory, those of alpha 2-adrenoceptor blocking agents are only weak. Therefore, a more selective alpha 2-adrenoceptor blocking agent is needed. In anaesthetized dogs and rats, (imidazolinyl-2)-2-benzodioxane 1-4 (170 150), a benzodioxane derivative, antagonized the pressor effects induced by adrenaline, noradrenaline and phenylephrine, but did not modify the effects of acetylcholine, histamine and isoprenaline.

Effects of nicergoline on the cardiovascular system of dogs and rats.

In pentobarbitalized closed-chest dogs, nicergoline (10--100 microgram/kg, i.v.) reduced blood pressure, heart rate, and splanchnic nerve activity.

Effects of some alpha-adrenoceptor agonists and antagonists on the guinea-pig ileum.

The purpose of the present study was to further characterize the alpha-adrenoceptors located on parasympathetic fibres. Segments of guinea-pig ileum were stimulated by transmural electrical pulses, and the ensuing contractions, which are due to the release of acetylcholine from postganglionic parasympathetic fibres, were monitored. Clonidine and tramazoline, which are thought to act preferentially on presynaptic alpha-adrenoceptors, reduced the contractions, whereas phenylephrine and methoxamine, postsynaptic alpha-adrenoceptor agonists, were ineffective.

[Pharmacologic study of several alpha-adrenolytics].

Six alpha-adrenoceptor blocking agents have been investigated in dogs and rats. 170 150 and 170 153 have been found the most potent of these agents. At low doses (0,1 microgram/kg) they reversed the pressor response to low doses of adrenaline (0,1 and 0,3 microgram/kg) and suppressed the response to high doses of adrenaline.

Pharmacological properties of AR-C239, 2-[2-[4(o-methoxyphenyl)-piperazine-1-Yl]-ethyl]4,4-dimethyl-1,3(2H-4H) isoquinolinedione, a new alpha-adrenoceptor blocking drug.

In pentobarbital-treated dogs and rats, AR-C239, a new and potent alpha-adrenoceptor blocking drug, competitively antagonized pressor responses to adrenaline and inhibited pressor responses to noradrenaline, phenylephrine, tyramine, and dimethylphenylpiperazinium. Injected intravenously into closed-chest dogs, AR-C239 (3-50 micrograms/kg) induced a progressive fall in blood pressure, heart rate, and sympathetic nerve activity. The drug appears to be devoid of direct vasodilator action, and the fall in blood pressure results from the peripheral alpha-blockade.

Effects of L-glutamic acid and kainic acid on central cardiovascular control.

L-Glutamic acid and kainic acid injected into the cisterna magna of dogs, produced a dose-dependent increase in blood pressure and a decrease in heart rate. In contrast, intravenous injection of both compounds was ineffective. The hypertension was probably due to an increase in sympathetic tone as guanethidine prevented the rise in blood pressure induced by central administration of L-glutamic acid and kainic acid.

Interactions between clonidine and alpha-adrenoceptor blocking drugs on the tachycardic response to stimulation of the cardiac nerve in dogs.

In pentobarbital-treated dogs clonidine (10 micrograms/kg) reduced the increase in heart rate caused by electrical stimulation of the cardiac nerve (1-10 Hz). We studied the actions of six alpha-adrenoceptor blocking drugs. Yohimbine (0.

[Action of N-butylnorsympathone on the effects of cardioaccelerator nerve stimulation in the dog].

In Dogs anaesthetized with pentobarbital (30 mg . kg-1), N-butylnorsympathone (20 mg . kg-1 i.

[Modification of the effect of cardio-accelerator nerve stimulation in dogs by clonidine and several alpha-adrenolytics].

In dogs anaesthetized with pentobarbital (30 mg. kg -1 i.v.