Antagonism of clonidine injected intracerebroventricularly in different models of salt intake

Clonidine, and alpha2-adrenergic agonist, injected into the brain inhibits salt intake of animals treated by the diuretic model of sodium depletion. In the present study, we address the question of whether central injection of clonidine also inhibits salt intake in animals deprived of water or in the need-free state. Saline or clonidine (30 nmol) was injected into the anterior third ventricle of 24-h sodium-depleted (furosemide + removal of ambient sodium), of 24-h water-deprived and of normovolemic (need-free state) adult male rats. Clonidine injected intracerebroventricularly (icv) inhibited the 1.5 per cent NaCl intake for 120 min by 50 to 90 per cent in every model tested. Therefore, different models of salt intake are inhibited by icv injection of clonidine. Idazoxan, an alpha2-adrenergic antagonist, injected icv at a dose of 160 nmol, inhibited the effect of clonidine only in the furosemide + removal of ambient sodium model of salt intake. This indicates that the antagonism of this effect by idazoxan is dependent on the body fluid/sodium status of the animal.

Effect of nifedipine, a calcium channel inhibitor, on sedation produced by reserpine, clonidine and propranolol in mice.

Spontaneous motor activity, rotarod test and observational rating of sedation were employed to study effect of nifedipine on sedation produced by reserpine, clonidine and propranolol. Reserpine (2 mg kg-1), clonidine (4 mg kg-1), and propranolol (40 mg kg-1) significantly reduced spontaneous motor activity and staying capacity of animals on accelerating rotarod (P < 0.01). Observational sedation was also caused significantly as indicated by a higher score in test. Nifedipine (2 mg kg-1) produced no sedation or excitation on its own. Reduction in spontaneous motor activity produced by reserpine and clonidine was partially reversed in animals treated with nifedipine (P < 0.01). A similar effect of nifedipine was also evident on the observational sedation induced by reserpine and clonidine. Effect of these drugs on rotarod times was nearly totally antagonised by nifedipine. Nifedipine did not oppose the sedation produced by propranolol which actually became significantly greater in the animals pretreated with nifedipine in all three tests. It is concluded that nifedipine antagonizes the sedation produced by reserpine and clonidine, probably by blocking central alpha 2-adrenoceptors. The sedative effect of propranolol can be potentiated by nifedipine possibly because of a pharmacokinetic interaction.

The effect of phentolamine on the pressor reponse to centrallly administered clonidine in rats

In the present study we investigae the effect of the previous injection of phentolamine (anonspecific alfa-adrenergic antagonist) into the lateral hypothalamus (LH) and lateral ventricle (LV) on the pressor and bradycardic responses produced by the injection of clonidine (an alfa-2 adrenergic agonist) into these same areas of conscious rats. The injections of clonidine into the LH produced pressor (39 ñ 5 and 38 ñ 3 mmHg, respectively) and bradycardic responses (-65 ñ 16 and -94 ñ 13 bpm, respectively). Previous injections of phentalamine into the LH or LV reduced the pressor response to clonidine injected into the same areas (DeltaMAP = 13 ñ 6 mmHg for LH and 1 ñ 3 mmHg for LV). No reduction was observed when clonidine was injected into the LV after the injection of phentalamine into the LH. No changes in bradycardic responses were observed after treatment with phentolamine. The present results show the participation of alfa-adrenergic receptors in the pressor response to centrally administered clonidine but not in the bradycardic reponse. The data also suggest that the pressor effect by the injection of clonidine into the LH is due to the activation of alfa-adrenergic receptors located specifically in this area. The pressor response after injection of clonidine into the LV and of phentolamine into the LH is due to the action of clonidine on other cerebral areas

Blockade by burimamide of the effects of clonidine on cardiac contractility phosphorylase activation and cyclic adenosine monophosphate in isolated guinea pig heart.

Clonidine in a dose-range of 2.5 microgram to 80 microgram caused positive inotropic effect, which was accompanied by increase in the cyclic AMP levels and phosphorylase-activation of the isolated perfused guinea pig heart. Clonidine-induced biochemical and mechanical effects were blocked by burimamide, an H2-receptor antagonist Propranolol (1 x 10(-6)M), phentolamine (1 x 10(-6)M) or reserpine pretreatment, did not affect the clonidine responses on the perfused guinea pig heart. Clonidine reduced the 4-methyl-histamine (H2-agonist) responses of guinea pig heart. Our data suggest that the cardiac effects of clonidine may be due to stimulation of H2-type of receptors.