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Quock RM, Beal GA, Chant ELF.
“Quipazine: a serotoninergic hyperthermic agent in the rabbit”.
J.Pharm.Pharmacol.. 1976;28:170-172.
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Abstract
Quipazine (2-(1-piperazinyl)-quinoline) was first described as a non-ergot oxytocic agent that might interact with serotoninergic (5-HT) mechanisms (Hong & Pardo, 1966). Subsequent research demonstrated that Quipazine did indeed stimulate serotoninergic receptors in both peripheral tissues (Hong, Sancillo & Vargas, 1969) and the central nervous system (Rodriguez, 1972; Rodriguez, Rojas-Ramirez B Druckcr-Colin, 1973). More recently, it has been reported that Quipazine blocks the uptake of 5-HT and dopamine into rat striatal tissue in vitro and, hence, might possess some anti-Parkinsonian potential (Medon, Leeling & Phillips, 1973). It has also been suggested that Quipazine might also interact with central dopaminergic systems since it induces behavioural symptoms in rats similar to those caused by dopaminergic agents; furthermore, these quipazine-induced responses were blocked by selective dopaminergic antagonists (Grabowska, Antkiewicz & Michaluk, 1974). Rabbit body temperature has been shown to increase in response to treatment with (+) - amphetamine (Hill & Horita, 1971), apomorphine (Hill & Horita, 1972) and other dopaminergic agonists (Quock, unpublished observations). Whether Quipazine produces a hyperthermic response in rabbits and whether this hyperthermia might be sensitive to antagonism by centrally-acting receptor blocking agents have now beets examined. - Male New Zealand rabbits, 2 0-2 5 kg, were restrained in open wooden stanchions (Shellenberger & Elder, 1967) while body temperature was electronically monitored and automatically recorded. Room temperature was constant at 22 0° 1 0°. Quipazine (Miles Laboratories), cyproheptadine (Merck Sharp & Dohme) and 3-(p-trifluoromethylphenoxy) - N-methyl-3-pllenylpropylamine hydrochloride (Lilly 110140) (Lilly) were prepared in aqueous solution immediately before injection. Haloperidol (McNeil Laboratories) and 2 - bromolysergic acid diethylamide (BO16-148) (Sandoz Pharmaceuticals) were acquired in pre-prepared ampules and diluted to appropriate concentrations with distilled water. All drug solutions were administered intravenously in a volume of 1.0 ml/ kg-1. In one experiment, intravenous administration of increasing doses of quipazine resulted in hyperthertnic responses of increasing magnitudes ([Fig. IA). Lethality was 50 % at 5 0 mg kg-1 and 100 % at 10 0 mg kg. After treatment with a standard dose of 2 5 mg kg-1, body temperature rose, reaching a peak at 2 h, and returned to base line after a further 5 h. Mydriasis was immediately evident after injection of the drug and lasted 1-2 h. An increased rate of respiration and constriction of the ear vasculature appeared within 15 min of injection and lasted about 3-4 h. Behaviourally, the animal became alert, assumed a standing rather than crouching posture and was instantly responsive to visual or auditory cues. There was no spontaneous body movement in these animals but the rabbits heads would immediately turn towards the direction of any sudden movement or sound. Rabbits injected with lethal doses of Quipazine exhibited similar behavioural and autonomic signs, eventually assuming a prostrate position with deep and rapid respiration. Behavioural excitation was not observed at any dose of quipazine.
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