Central Effects of Clonidine 2‐(2,6‐dichlorophenylamino)‐2‐imidazoline Hydrochloride in Fowls

Abstract

1 The effects of clonidine infused into the IIIrd cerebral ventricle, the hypothalamus or intravenously were studied on behaviour, electrocortical activity, body, comb and leg temperatures, respiration and carbon dioxide elimination in adult and young fowls (Gallus domesticus). 2 Behavioural and electrocortical slow wave sleep were induced by clonidine infused into IIlrd cerebral ventricle, the hypothalamus or intravenously. Surprisingly, sleep elicited by intravenous clonidine was much longer-lasting than that induced by an identical dose given intraventricularly. 3 Body temperature was lowered by clonidine given intraventricularly or infused into the hypothalamus. Depending on initial comb temperature and ambient temperature, comb temperature was elevated, unaffected or lowered as body temperature fell; temperature of the unfeathered legs also rose as body temperature declined after clonidine. 4 Following clonidine, but before any considerable decline of body temperature, tachypnoea and wing abduction developed; during recovery of body tenmperature, the wings were lowered and applied closely to the trunk and the feathers partly erected. 5 CO2 elimination fell more swiftly than body temperature following intrahypothalamic clonidine in young chicks; initial recovery developed sooner than that of body temperature, but eventual recovery was delayed compared to that for body temperature. The effects of clonidine were much more marked in young chicks studied at an ambient temperature below thermoneutrality as compared to thermoneutrality. 6 The soporific effects of clonidine were attenuated by intraventricular phentolamine; its hypothermic effects were prevented by phenoxybenzamine and prevented or attenuated by phentolamine. Intraventricular atropine, haloperidol, methysergide and propranolol were ineffective. 7 Larger doses of intraventricular phentolamine elicited shivering, tachypnoea and wing abduction; body temperature was elevated, to the extent even of lethal hyperthermia. Intraventricular atropine also elevated body temperature. 8 Clonidine infused intravenously, intraventricularly or into the hypothalamus, replaced the behavioural and electrocortical arousal evoked with dexamphetamine, by sleep associated with slow wave electrocortical activity.

The Pharmacology of Clonidine and Related Products

“…In rats a depression in respiration has been reported and it was suggested to be due to the stimulation of central (X adrenoceptors (BOLME and FUXE, 1973). In adult fowls clonidine was shown to cause tachypnea (MARLEY and NISTICO, 1975). LAUBIE and SCHMITT (1969) did not find any change in total oxygen consumption or carbon dioxide production in renal hypertensive dogs anesthetized with pentobarbital, but MAXWELL (1969) reported a decrease in both values in chloralosed dogs.…”

Further investigation of anticoccidial activity of 7-bromo-N-(2-imidazolidinylidene)-1H-indazol-6-amine

“…Tumor necrosis factor a, in turn, has been shown to have antiprotozoal effects against intracellular parasites such as T. cruzi (5) and Plasmodium yoelii (24). Another effect of clonidine is to lower body temperature (12), which may be significant, since E. tenella does not grow in tissue culture at temperatures much below the body temperature of chickens. Physiological processes known to be under a adrenergic control include gut motility (25), intestinal blood flow (1), electrolyte balance (14), and many others.…”

Clonidine: New research in psychotropic drug pharmacology

“…83 Behavioral and electrocortical sleep induced by intraventricular administration of clonidine (5-15 pg) was interrupted easily by an arousing stimulus77 and presentation of sensory stimuli during clonidine-induced sleep induced behavioral and phasic electrocortical arousal. 79 In conclusion, a number of studies have demonstrated a sedative or sleep-inducing action of clonidine. These investigations suggest that the sleep-inducing effect of clonidine occurs through a stimulatory action of this drug at central a-noradrenergic r e~e p t o r s .~8 ,~~ It does not appear that the sleep-inducing action of clonidine depends on serotonergic t r a n s m i~s i o n .~~…”