Sleep produced by clonidine (2-(2,6-dichlorophenylamino)-2-imidazoline hydrochloride) |
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| Authors: | R B Holman E E Shillito M Vogt |
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| Abstract: | 1. The dose of clonidine (given intravenously) required to elicit sleep in the young chick is 1/25th to 1/50th of an equiactive dose of noradrenaline. The approximate ED50 is 0.01 mumol/kg. Phentolamine (10-15 mg/kg, but not 5 mg/kg) antagonizes the action of both clonidine and noradrenaline.2. Intensive treatment with p-chlorophenylalnine (700 mg/kg for 3-4 days) does not prevent the hypnotic effect of clonidine in the chick, although brain 5-HT is reduced to 15% of normal. Neither is natural sleep modified.3. Sleep after clonidine is not affected by methysergide (0.1-1 mumol/kg, i.m.), but prevented by LSD (0.1-0.3 mumol/kg). The effect of LSD is interpreted as a physiological antagonism.4. Clonidine (50 mg/kg) injected intravenously into adult rats causes sleep which is not abolished by phentolamine (5 mg/kg) or by p-chlorophenylalanine in doses which interfere with natural sleep.5. When, per kg body weight, the same dose of clonidine is injected into the lateral cerebral ventricle of rats, sleep ensues in more than half the animals, and persistent eating in about a third; only one of seventeen rats showed no change in behaviour. Eating and sleeping remained unaltered after p-chlorophenylalanine. The actual dose of clonidine injected into the lateral ventricle was 0.037 mumol, amounting to about 0.15 mumol/kg or 15 times the dose required intravenously in the chick. Noradrenaline 0.15 mumol per (intraventricular) injection caused eating but no sleep, whereas higher doses produced ataxia and paresis.6. The work suggests that clonidine does not elicit sleep by an action requiring the integrity of the 5-HT-containing neurones arising in the raphé nuclei, and that its action is not on tryptamine receptors. In the chick, sleep appears to be produced by a central sympathomimetic effect; it is possible, but not certain, that this also holds for the rat.7. The intravenous hypnotic dose of clonidine for the cat is about the same as that for the rat, but injection is not accompanied by signs of peripheral sympathetic stimulation. |
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