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Effects of lisuride on body temperature of rats and rabbits: Relation to microsomal biotransformation and dopaminergic receptor stimulation

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Abstract

In rats, lisuride, either administered systemically or intracerebroventricularly induced a doserelated hypothermia. This effect was selectively antagonized by blockade of DA receptors in the CNS but not by inhibition of catecholamine synthesis or blockade of serotoninergic receptors. Also a blocker of “peripheral” DA receptors failed to antagonize the hypothermic effect of lisuride in rats. Induction of rat liver microsomal drug-metabolizing enzymes by phenobarbital counteracted lisuride-induced hypothermia. In rabbits lisuride induced a hyperthermic response which was sensitive to both pimozide and metergoline pretreatment. These findings indicate that stimulation of brain DA receptors involved in thermoregulation is responsible for the changes in body temperature induced by lisuride in rats and rabbits and that these effects are caused by the drug itself and do not require previous biotransformation into an active metabolite.

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References

  • Altaffer FB, De Balbian Verster F, Hall S, Lang CJ, D'Encarnacao P (1970) A simple and inexpensive cannula technique for chemical stimulation of the brain. Psychiol Behav 5:119–121

    Google Scholar 

  • Andén NE, Butcher SG, Corrodi H, Fuxe K, Ungerstedt U (1970) Receptor activity and turnover of dopamine and noradrenaline after neuroleptics. Eur J Pharmacol 11:303–314

    Google Scholar 

  • Barnett A, Goldstein J, Taber RI (1972) Apomorphine-induced hypothermia in mice: a possible dopaminergic effect. Arch Int Pharmacodyn Ther 198:242–247

    Google Scholar 

  • Baumgarten HG, Lachenmayer L, Schlossberger HG (1972) Evidence for a degeneration of indoleamine-containing nerve terminals in rat brain induced by 5,6-dihydroxytryptamine. Zellforsch Mikrosk Anat 125:553–569

    Google Scholar 

  • Beretta C, Ferrini R, Glösser AH (1965) 1-Methyl-8-β-carbo-benziloxy-aminometil-10-α-ergoline, a potent and long-lasting 5-hydroxytryptamine antagonist. Nature 207:421–422

    Google Scholar 

  • Bornstein DL, Bredenberg C, Wood WB (1963) Studies on the pathogenesis of fever XI. Quantitative features of the febrile response to leucocytic pyrogen. J Exp Med 117:349–364

    Google Scholar 

  • Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Bunney WE Jr (eds) Pre- and postsynaptic receptors, Annual ACNP Meeting, Puerto-Rico. Dekker, New York, p 49

    Google Scholar 

  • Carruba MO, Bächtold HP (1976) Pyrogen fever in rabbits pretreated with p-chlorophenylalanine or 5,6-dihydroxytryptamine. Experientia 32:729–730

    Google Scholar 

  • Carruba MO, Tofanetti O, Picotti GB, Mantegazza P (1978) Involvement of serotoninergic neurons in the hyperthermic response to dopaminergic agonists. Pharmacol Res Commun 10:357–370

    Google Scholar 

  • Carruba MO, Ricciardi S, Müller EE, Mantegazza P (1980) Anorectic effect of lisuride and other ergot derivatives in the rat. Eur J Pharmacol 64:133–141

    Google Scholar 

  • Cox B, Lee TF (1977) Do central dopamine receptors have a physiological role in thermoregulation. Br J Pharmacol 61:83–86

    Google Scholar 

  • Da Prada M, Bonetti EP, Keller HH (1977) Induction of mounting behaviour in female and male rats by lisuride. Neuroscience Lett 6:349–353

    Google Scholar 

  • Ernst AM (1967) Mode of action of apomorphine and dexamphetamine on gnawing compulsion in rats. Psychopharmacologia 10:316–323

    Google Scholar 

  • Feldberg W, Lotti VJ (1967) Temperature responses to monoamines and an inhibitor of MAO injected into the cerbral ventricles of rats. Br J Pharmacol 31:152–161

    Google Scholar 

  • Fujita N, Saito K, Yonehara N, Yoshida H (1978) Lisuride inhibits 3H-spiroperidol binding to membranes isolated from striatum. Neuropharmacology 17:1089–1091

    Google Scholar 

  • Fuxe K, Sjöqvist F (1972) Hypothermic effect of apomorphine in the mouse. J Pharm Pharmacol 24:702–705

    Google Scholar 

  • Gräf K-J, Neumann F, Horowski R (1976) Effect of the ergot derivative lisuride hydrogen maleate on serum prolactin concentrations in female rats. Endocrinology 98:598–605

    Google Scholar 

  • Herrmann WM, Horowski R, Damrehl K, Kramer V, Lurati K (1977) Clinical effectiveness of lisuride hydrogen maleate: a double-blind trial versus methysergide. Headache 17:54–60

    Google Scholar 

  • Hill H, Horita A (1972) A primozide-sensitive effect of apomorphine on body temperature of the rabbit. J Pharm Pharmac 24:490–491

    Google Scholar 

  • Horowski R, Neumann F, Gräf K-J (1975) Influence of apomorphine hydrochloride, dibutyryl-apomorphine hydrochloride, dibutyryl-apomorphine, and lysenyl on plasma prolactin concentrations in the rats. J Pharm Pharmacol 27:532–533

    Google Scholar 

  • Horowski R, Wachtel H (1976) Direct dopaminergic action of lisuride hydrogenmaleate, an ergot derivative, in mice. Eur J Pharmacol 36:373–383

    Google Scholar 

  • Horowski R (1978) Differences in the dopaminergic effects of the ergot derivatives bromocrptine, lisuride, and d-LSD as compared with apomorphine. Eur J Pharmacol 51:157–166

    Google Scholar 

  • Horowski R (1979) Hypothermic action of lisuride in rats and differences to bromocriptine in the antagonistic effect of neuroleptics. Naunyn Schmiedebergs Arch Pharmacol 306:147–151

    Google Scholar 

  • Kato R, Chiesara E, Vassanelli P (1964) Further studies on the inhibition and stimulation of microsomal drug metabolizing enzymes of rat liver by various compounds. Biochem Pharmacol 13:69–83

    Google Scholar 

  • Kebabian JW, Kebabian PR (1978) Lergotrile and lisuride: in vivo dopaminergic agonists which do not stimulate the presynaptic dopamine autoreceptor. Life Sciences 23:2199–2204

    Google Scholar 

  • Kehr W, Carlsson A, Linquist M (1975) Biochemical aspects of dopamine agonists. In: Calne D, Chase TN, Barbeau A (eds) Dopaminergic mechanisms. Raven, New York, p 185

    Google Scholar 

  • Kehr E (1977) Effects of lisuride and other ergot derivatives on monoaminergic mechanisms in rat brain. Eur J Pharmacol 41:261–273

    Google Scholar 

  • Keller HH, Da Prada M (1979) Central dopamine agonistic activity and microsomal botransformation of lisuride, lergotrile, and bromocriptine. Life Sci 24:1211–1222

    Google Scholar 

  • Koe BK, Weissman A (1966) p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther 154:499–516

    Google Scholar 

  • Kruk ZL (1972) The effect of drugs acting on dopamine receptors on the body temperature of the rat. Life Sci 11:845–850

    Google Scholar 

  • Liuzzi A, Chiodini PG, Oppizzi G, Botalla L, Verda G, De Stefano L, Colussi G, Gräf K-J, Horowski R (1978) Lisuride hydrogen maleate: evidence for a long lasting dopaminergic activity in humans. J Clin Endocrinol Metab 46:196–202

    Google Scholar 

  • Marley E, Nistico G (1972) Effects of catecholamines and adenosine derivatives given into the brains of fowls. Br J Pharmacol 46:619–636

    Google Scholar 

  • McDevitt JT Jr, Setler PE (1978) Evidence relating the dopamine agonist activity of lergotrile to its conversion into an active metabolite. Fed Proc 37:855

    Google Scholar 

  • Orrenius S, Ericsson JLE, Ernster L (1965) Phenobarbital-induced synthesis of the microsomal drug-metabolizing enzyme system and its relationship to the proliferation of endoplasmic membranes. A morphological and biochemical study. J Cell Biol 25:627–639

    Google Scholar 

  • Pieri L, Keller HH, Burkard W, Da Prada M (1978a) Effects of lisuride and LSD on cerebral monoamine systems and hallucinosis. Nature 272:278–280

    Google Scholar 

  • Pieri M, Schaffner R, Pieri L, Da Prada M, Haefely W (1978b) Turning in MFB-lesioned rats and antagonism of neuroleptic-induced catalepsy after lisuride and LSD. Life Sci 22:1615–1622

    Google Scholar 

  • Quock RM, Gale CC (1974) Hypothermia mediating dopamine receptors in the preoptic anterior hypothalamus of the cat. Naunyn Schmiedebergs Arch Pharmacol 285:297–300

    Google Scholar 

  • Reyntjens AJ, Niemegrees CJE, Von Neuten JM, Laduron P, Heykants J, Schellekens HL, Marsboon R, Jagenau A, Brockaert A, Janssen PAJ (1978) Domperidone, a novel and safe gastrokinetic anti-nauseant for the treatment of dispepsia and vomiting. Arzneim. Forsch 28:1194–1198

    Google Scholar 

  • Schelkunov EL, Stabrovsky EM (1971) Relationship between depletion of norepinephrine in the brain and the hypothermic effect of apomorphine in mice. Farmakol Toksikol 34:653–657

    Google Scholar 

  • Shellenberger MK, Elder JT (1967) Changes in rabbit core temperature accompanying alterations in brain stem monoamine concentrations. J Pharmacol Exp Ther 158:219–226

    Google Scholar 

  • Sibergeld EK, Adler J, Calne DB (1977) The roles of presynaptic function and hepatic drug metabolism in the hypothermic actions of two novel dopaminergic agonists. J Pharm Pharmacol 29:632–635

    Google Scholar 

  • Spector S, Sjoerdsma A, Udenfriend S (1965) Blockade of endogenous norepinephrine synthesis by α-methyl-tyrosine, an inhibitor of tyrosine hydroxylase. J Pharmacol Exp Ther 147:86–95

    Google Scholar 

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Carruba, M.O., Ricciardi, S., Negreanu, J. et al. Effects of lisuride on body temperature of rats and rabbits: Relation to microsomal biotransformation and dopaminergic receptor stimulation. Psychopharmacology 70, 223–229 (1980). https://doi.org/10.1007/BF00427878

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  • DOI: https://doi.org/10.1007/BF00427878

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