Pharmakologische Beeinflussungsmöglichkeiten der Tremorin- und Arecolin-Hypothermie

Abstract

Both tremorine and arecoline cause a drop in body temperature in small laboratory animals (mice, rats, guinea pigs) as well as tremor, rigor and peripheric effects. The purpose of this paper is (1) to characterize the up-until-now unknown hypothermic effect of arecoline, as compared with tremorine, and (2) to check the action of drugs used in Parkinson's disease and others on this hypothermia in mice in order to obtain information on the action of tremorine and arecoline on thermoregulation and on their antagonists. The relations between dose and body temperature of male mice kept at different ambient temperatures after intraperitoneal injection of arecoline or tremorine and the influences of antagonists (in view of tremor) on hypothermia have been studied. The hypothermic action following the use of tremorine is more continuous and more pronounced than that following arecoline. Judged by the same degree of body temperature depression, the effect of tremorine is five to 10 times stronger than that of arecoline. Scopolamine, atropine, benactycine and trihexyphenidyl block the hypothermic effect of tremorine and arecoline; hypothermia after arecoline is not influenced by caramiphen; antiparkin, butylscopolamine, as well as the phenothiazine-derivatives ethopropazine, promethazine and diethazine, are also ineffective; methylatropine reduces the arecoline-hypothermia only in high doses. Hypothermia after arecoline and tremorine is mainly based on a central action. The effects of several central cholinolytics and the antihypothermic inefficiency of phenothiazines, used in Parkinson's disease and against motoric effects of tremorine and arecoline, demonstrate a difference within this group of drugs. The trigger in hypothermic action is a cholinergic one.

Zusammenfassung

• 1. Arecolin ruft bei Mäusen, Ratten und Meerschweinchen eine der Tremorinhypothermie vergleichbare Senkung der Körpertemperatur hervor.

• 2. Die hypothermiewirksamen Dosen des Arecolins sind bei der Maus in Abhängigkeit von der Umgebungstemperatur bei intraperitonealer Gabe 5- bis 10mal höher als die isoeffektiven Tremorindosen.

• 3. Der Hypothermieeffekt beider Stoffe kann dosisabhängig durch Atropin, Scopolamin, Benactycin und Trihexyphenidyl gehemmt werden.

• 4. Die arecolin- und tremorinbedingte Hypothermie wird durch auf die motorischen Effekte beider Stoffe hemmend wirkende Phenothiazine Diaethazin, Promethazin und Aethopropazin nicht vermindert.

• 5. Die nur in hohen Dosen in das Zentralnervensystem eindringenden quaternären Verbindungen Methylatropin und Butylscopolamin beeinflussen in Dosierungen, die mit den wirksamen Mengen von Atropin und Scopolamin vergleichbar sind, die Senkung der Körpertemperatur hingegen nicht.

• 6. Arecolin- und Tremorinhypothermie werden vorwiegend zentral über einen cholinergen Mechanismus ausgelöst.