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Behavioral and neurochemical profiles of discriminant benzamide derivatives

Published online by Cambridge University Press:  28 April 2020

P. Sokoloff ,
M.-P. Martres ,
K. Redouane ,
J.-C. Schwartz ,
P. Protais ,
M. Vasse ,
I. Dubuc ,
J. Costentin ,
P. Hamdi  and
A. Mann
...Show all authors
P. Sokoloff
Affiliation:
Unité 109 de Neurobiologie et Pharmacologie, Centre Paul Broca de l’INSERM, 2 ter rue d’Alésia, 75014Paris, France
M.-P. Martres
Affiliation:
Unité 109 de Neurobiologie et Pharmacologie, Centre Paul Broca de l’INSERM, 2 ter rue d’Alésia, 75014Paris, France
K. Redouane
Affiliation:
Unité 109 de Neurobiologie et Pharmacologie, Centre Paul Broca de l’INSERM, 2 ter rue d’Alésia, 75014Paris, France
J.-C. Schwartz*
Affiliation:
Unité 109 de Neurobiologie et Pharmacologie, Centre Paul Broca de l’INSERM, 2 ter rue d’Alésia, 75014Paris, France
P. Protais
Affiliation:
UA 1170 du CNRS, Unité de Neuropsychopharmacologie Expérimentale, U.E.R. de Médecine et Pharmacie, Avenue de l’Université, 76800St-Etienne du Rouvray, France
M. Vasse
Affiliation:
UA 1170 du CNRS, Unité de Neuropsychopharmacologie Expérimentale, U.E.R. de Médecine et Pharmacie, Avenue de l’Université, 76800St-Etienne du Rouvray, France
I. Dubuc
Affiliation:
UA 1170 du CNRS, Unité de Neuropsychopharmacologie Expérimentale, U.E.R. de Médecine et Pharmacie, Avenue de l’Université, 76800St-Etienne du Rouvray, France
J. Costentin
Affiliation:
UA 1170 du CNRS, Unité de Neuropsychopharmacologie Expérimentale, U.E.R. de Médecine et Pharmacie, Avenue de l’Université, 76800St-Etienne du Rouvray, France
P. Hamdi
Affiliation:
Centre de Neurochimie, Laboratoire de Pharmacochimie Moléculaire, ERA 393 du CNRS, Strasbourg, France
A. Mann
Affiliation:
Centre de Neurochimie, Laboratoire de Pharmacochimie Moléculaire, ERA 393 du CNRS, Strasbourg, France
C.G. Wermuth
Affiliation:
Centre de Neurochimie, Laboratoire de Pharmacochimie Moléculaire, ERA 393 du CNRS, Strasbourg, France
*
Corresponding author: J.-C. Schwartz Correspondance à adresser à
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Summary

Discriminant benzamide derivatives (DBD), the prototype of which is DO 710 i.e. N- [(1-propyl 2-pyrrolidinyl) methyl] 5-methyl sulfamoyl 2-methoxy benzamide, were compared to classical neuroleptics such as haloperidol in various behavioral and biochemical tests. Whereas the ID50 (or ED50) of haloperidol for antagonising various apomorphine-induced behavioral responses and producing catalepsy in rats were all around 0.1 mg/kg. DO 710 clearly distinguished catalepsy, HVA increase and apomorphine-induced licking and sniffing in rats (for which the ED50 (or ID50) were 13-54 mg/kg) from apomorphine-induced climbing, yawning and hypothermia (for which the ID50 were 1-2 mg/kg) (fig. 1, 2 and 4). Moreover, DO 710 and other DBD potentiated stereotypies in mice, whereas haloperidol and other classical neuroleptics did not (fig. 3). These features do not seem to be attributable to a heterogenous distribution of DBD in brain, since their ED50 for HVA increase and for inhibiting 3H-N-propylnorapomorphine binding in vivo did not differ in striatum and in limbic regions.

In in vitro binding experiments, DO 710 and other DBD discriminated two classes of 3H-domperidone binding sites in striatum, whereas only one component with a relatively low affinity for DBD could be detected in pituitary (fig.5-6, Table 3). 3H-DO 710 allowed charaterization of a D-2 site with a low affinity for DBD, which was fully sensitive to GTP regulation and present in pituitary and brain, and of a “D-4” site, preferred by DBD, which was little or not sensitive to GTP, present in brain and particularly enriched in olfactory bulb but absent in pituitary (fig. 7). 3H -azidosulpride (i.e. N-[(1-3H- propyl 2-pyrrolidinyl) methyl] 2-methoxy 4-azido 5-methylsulfamoyl benzamide), a photoactivable analog of 3H-DO 710, was used for irreversible labelling of dopamine recognition sites. When subjected to SDS-PAGE, receptor from striatum, pituitary and olfactory bulb co-migrated as a single band of 85 kDa (fig. 8).

These results may suggest the existence of two subclasses of dopamine D-2 receptor as targets for neuroleptic actions, one being preferred by DBD. The recognition subunits of these receptors have similar apparent molecular size.

Résumé

Résumé

Les dérivés benzamides substitués discriminants (DBD) dont le prototype est le DO 710 : N- [(propyl-1 pyrrolidinyl-2) méthyl] méthoxy-2 méthylsulfamoyl-5 benzamide, ont été comparés à des neuroleptiques classiques comme le halopéridol dans divers tests comportementaux et biochimiques. Alors que les DE50 (ou DI50) du halopéridol pour antagoniser les réponses comportementales induites par l’apomorphine et pour produire la catalepsie chez le rat sont toutes voisines de 0.1 mg/kg, le DO 710 distingue clairement la catalepsie, l'augmentation d'HVA et les léchements et reniflements chez le rat (pour lesquels les DE50 (ou DI50) sont de 13 à 54 mg/kg) de la verticalisation, des baillements et de l’hypothermie induits par l’apomorphine (pour lesquels les DI50 sont de 1 à 2 mg/kg) (Fig. 1, 2 et 4). Le DO 710 et d’autres DBD potentialisent les stéréotypies chez la souris, alors que les neuroleptiques classiques n’ont pas cette propriété (Fig. 3). Ce profil pharmacologique original des DBD ne semble pas être du ci une distribution hétérogène de ces composés dans le cerveau, car leur DE50 Pour accroître l'HVA et pour inhiber la liaison in vivo de N propylnorapomorphine - 3H ne different pas dans le striatum et les régions limbiques.

Dans les études de liaison in vitro, le DO 710 et les DBD discriminent deux populations de sites de liaison du dompéridone - 3H dans le striatum, alors que seule la population de sites à basse affinité pour les DBD est détectable dans l’hypophyse antérieure (Fig. 5, 6 et Tableau 3).

Le DO 710-3H a permis de caractériser un site D-2 à relativement basse affinité pour les DBD, complètement sensible à la régulation par le GTP, présent dans l'hypophyse et le cerveau et un site “D-4”, présentant une meilleure affinité pour les DBD, peu ou pas sensible au GTP, présent dans le cerveau et plus particulièrement enrichi dans le bulbe olfactif mais absent de l’hypophyse (Fig. 7).

L’azidosulpride -3H i.e. N-[(propyl -3H-1 pyrrolidinyl - 2)méthyl] méthoxy-2 méthylsulfamoyl-5 azido-4 benzamide, un analogue photoactivable du DO 710 a été utilisé pour marquer irréversiblement les récepteurs dopaminergiques. Les récepteurs du striatum, de l’hypophyse et du bulbe olfactif ainsi marqués et soumis à une électrophorèse en SDS sur gel de polyacrylamide co-migrent en une seule bande de 85 KDa (Fig. 8).

Ces résultats suggèrent l'existence de deux sous-types de récepteurs dopaminergiques D-2, dont le blocage préférentiel de l’un d’entre eux par les DBD explique leurs propriétés particulières. Les deux récepteurs ont un site de reconnaissance de taille moléculaire apparente identique.

Keywords

D-2 dopamine receptorsBenzamideBehaviorLigand binding assayPhotoaffinity labellingRécepteurs dopaminergiques D-2Dérivé benzamideComportementLiaison in vitroMarquage par photoaffinité
Type
Research Article
Information
Psychiatry and Psychobiology , Volume 2 , Issue 4 , 1987 , pp. 253 - 263
Copyright
Copyright © European Psychiatric Association 1987

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References

References/Bibliographie

Amlaiky, N., Caron, M.G. - Photoaffinity labeling of the D-2 dopamine receptor using a novel high affinity radioiodinated probe. J Biol Chem 1985; 260: 1983–1986.Google Scholar
Anden, N.E., Stock, G. - Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic System. J Pharm Pharmacol 1973; 25: 346–338.CrossRefGoogle ScholarPubMed
Barghon, R., Protais, P., Colboc, O., Constentin, J. - Hypokinesia in mice and catalepsy in rats elicited by morphine associated with antidopaminergic agents including atypical neuroleptics. Neurosci Lett 1981; 27: 69–73.CrossRefGoogle ScholarPubMed
Costentin, J., Protais, P., Schwartz, J.C. - Rapid and dissociatcd changes in the sensitivities of different dopamine receptors in mouse brain. Nature 1975; 257: 405–407.CrossRefGoogle ScholarPubMed
Davis, A. - Determination of the hydrodynamic properties of detergent-solubilised proteins. In: Venter, J.C., Harrison, L.C. eds: Molecular and chemical characterization of membrane receptors, 161–178, Alan R. Liss, Inc., New York, 1984.Google Scholar
De Lean, A., Kilpatrick, B.F., Caron, M.G. - Dopamine receptors of the porcine anterior pituitary gland - evidence for two affinity States discriminated by both agonists and antagonists. Mol Pharmacol 1982; 22: 290–297.Google ScholarPubMed
Dubuc, I., Protais, P., Colboc, O., Costentin, J. - Antagonism of apomorphine-induced yawning by “atypical neuroleptics”. Psychopharmacol 1982; 21: 1203–1206.Google ScholarPubMed
Enjalbert, A., Bockaert, J. - Pharmacological characterization of the D-2 dopamine receptor negatively coupled with adenylate cyclase in rat anterior pituitary. Mol Pharmacol 1983; 23: 576–584.Google Scholar
Euvrard, C., Ferland, L., Di Paolo, T., Beaulieu, M., Labrie, F., Oberlander, C., Raynaud, J.P., Boissier, J.R. - Activity of two new potent dopaminergic agonists at the striatal and anterior pituitary levels. Neuropharmacol 1980; 19: 379–386.CrossRefGoogle ScholarPubMed
Freedman, S.B., Poat, J.A., Woodruff, G.N. - Effect of guanine nucleotides on dopaminergic agonist and antagonist affinity for 3H-sulpiride binding sites in rat striatal membrane preparations. J Neurochem 1981; 37: 608–612.CrossRefGoogle ScholarPubMed
Fuxe, K., Agnati, L.F., Andersson, K., Calza, L., Benfenati, F., Zini, I., Battistini, N., Kohler, C., Ogren, S.O., Hokfelt, T. - Analysis of transmitter identifted neurons by morphometry and quantitative microfluorimetry. Evaluation of the actions of psychoactive drugs, especially sulpiride. In: Ackenheil, M., Matussek, N. eds : Special aspects of psychopharmacology, 13–34, Expansion Scientifique Française, 1983.Google Scholar
Gulat-Marnay, C., Lafitte, A., Schwartz, J.C. - Effect of discriminant and non-discriminant dopamine antagonists on in vivo binding of 3H-propylnorapomorphine in mouse striatum and tuberculum olfactorium. Naunyn Schmiedeberg's Arch Pharmacol 1985; 329: 117–122.CrossRefGoogle Scholar
Harnryd, C., Bjerkenstedt, L., Bjork, K., Gullberg, B., Oxen-Stierna, G., Sedvall, G.Wiesel, F.A., Wik, G., Aberg-Wistedt, A. - Clinical evaluation of sulpiride in schizophrenic patients. A double blind comparison with chlorpromazine. In: Sedvall, G. ed: The use of substituted benzamides in psychiatry, 7–30, Proceedings of a symposium held during the 13th CINP Congress, Jerusalem, 1982.Google Scholar
Kebabian, J.W., Calne, D.B. - Multiple receptors for dopamine. Nature 1979; 277: 93–96.CrossRefGoogle ScholarPubMed
Leeb-Lundberg, L.M.F., Dickinson, K.E.J., Heald, S.L., Wikberg, J.E.S., Hagent, P.O., Debernardis, J.F., Winn, M., Arendsen, D.L., Lefkowitz, J., Caron, M.G. - Photoaffinity labeling of mammalian alpha 1-adrenergic receptors. Identification of the ligand binding subunit with a high affinity radioiodinated probe. J Biol Chem 1984; 259: 2579–2587.Google ScholarPubMed
Lilly, L., Fraser, C.M., Jung, C.Y., Seeman, P., Venter, J.C. - Molecular size of the canine and human brain D-2 dopamine receptor as determined by radiation inactivation. Mol Pharmacol 1983; 24: 10–14.Google Scholar
Maneckjee, R., Zuckin, R.S., Archer, S., Michael, J., Osei-Gyimah, P. - Purification and characterization of the mu opiate receptor from rat brain using affinity chromatography. Proc Natl Acad Sci 1985; 82: 594–598.CrossRefGoogle ScholarPubMed
Martres, M.P., Sokoloff, P., Delandre, M., Schwartz, J.C., Protais, P., Costentin, J. - Selection of dopamine antagonists discriminating various behavioral responses and radioligand binding sites. Naunyn Schmiedeberg's Arch Pharmacol 1984; 325: 102–115.CrossRefGoogle ScholarPubMed
Mizuchi, A., Kitakawa, N., Miyachi, Y. - Regional distribution of sultopride in rat brain measured by radioimmunoassay. Psychopharmacology 1983; 81: 195–198.CrossRefGoogle ScholarPubMed
Moore, K.E., Kelly, P.H. - Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons. In: Lipton, M.A., Di Mascio, A., Killam, K.F. eds: Psychopharmacology: a generation of progress, 221–234, Raven Press, New York, 1978.Google Scholar
Munemura, M., Cote, T.E., Tsuruta, K., Eskay, R.L., Kebabian, J.W. - The dopamine receptor in the intermediate lobe of the rat pituitary gland: pharmacological characterization. Endocrinology 1980; 107: 1676–1683.CrossRefGoogle ScholarPubMed
Munk-Andersen, E., Behnke, K., Heltberg, J., Nielsen, H., Gerlach, J. - Sulpiride versus haloperidol, a clinical trial in schizophrenia. A preliminary report. In: Sedvall, G. ed.: The use of substituted benzamides in psychiatry, 31–42, Proceedings of a symposium held during the 13th CINP-Congress, Jerusalem, 1982.Google Scholar
Nielsen, M., Klimek, V., Hyttel, J. - Distinct target size of dopamine D-l and D-2 receptors in rat striatum. Life Sci 1984; 35: 325–332.CrossRefGoogle Scholar
Onalli, P., Schwartz, J.P., Costa, E. - Dopaminergic modulation of adenylate cyclase stimulation by vasoactive intestinal peptide in anterior pituitary. Proc Natl Acad Sci 1981; 78: 6531–6534.CrossRefGoogle Scholar
Protais, P,, Dubuc, I., Costentin, J. - Pharmacological characteristics of dopamine receptors involved in the dual effects of dopamine agonists on yawning behaviour in rats. Eur J Pharmacol 1983; 94: 271–280.CrossRefGoogle ScholarPubMed
Protais, P., Vasse, M., Dubuc, L, Costentin, J., Sokoloff, P., Martres, M.P., Redouane, K., Schwartz, J.C., Bouthenet, M.L., Sales, N., Hamdi, P., Mann, A., Wermuth, C. - Dopaminergic behavioral responses and classes of binding sites distinguished by discriminant benzamide derivatives. In: Woodruff, G.N., Poat, J.A., Roberts, P.J., eds.: Dopaminergic Systems and their regulation, 131–152, McMillan Press, 1986.CrossRefGoogle Scholar
Protais, P., Bonnet, J.J., Costentin, J., Schwartz, J.C. - Rat climbing behavior elicited by stimulation of cerebral dopamine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 1984; 325: 93–101.CrossRefGoogle ScholarPubMed
Quach, T.T., Duchemin, A.M., Rose, C., Schwartz, J.C. - In vivo binding of 3H-mepyramine in mouse brain: correlation between occupation of central H1-receptors of histamine and sedative properties of various psychotropic drugs. Eur J Pharmacol 1979; 60: 391–392.CrossRefGoogle Scholar
Redouane, K., Sokoloff, P., Schwartz, J.C., Hamdi, P., Mann, A., Wermuth, C.G., Roy, J., Morgat, J.L. - Photoaffinity labeling of D-2 dopamine binding subunits from rat striatum, anterior pituitary and olfactory bulb with a new probe, 3H-azidosulpride. Biochem Biophys Res Commun 1985; 130: 1086–1092.CrossRefGoogle ScholarPubMed
Schwartz, J.C., Sokoloff, P., Martres, M.P., Protais, P., Costentin, J., Bouthenet, M.L., Sales, N. - Distinction of dopamine receptors well recognised by antipsychotic agents: binding, autoradiographic and behavioural studies. In: Carlsson, A., Lars, J., Nilsson, G. eds.: Dopamine receptor agonists, 47–59, Acta Pharmaceutica Suecica, Swedish Pharmaceutical Press, Stockholm, 1983.Google Scholar
Schwartz, J.C., Delandre, M., Martres, M.P., Sokoloff, P., Protais, P., Vasse, M., Costentin, J., Laibe, P., Wermuth, C.G., Gulat, C., Laffite, A. - Biochemical and behavioral identification of discriminant benzamide derivatives: new tools to differentiate subclasses of dopamine receptors. In: Usdin, E., Carlsson, A., Dahlstrom, A., Engel, J. eds.: Catecholamines: neuropharmacology and Central Nervous System - Theoretical aspects, 59–72. Alan R. Liss, Inc. New York, 1984.Google Scholar
Seeman, P. - Brain dopamine receptors. Pharmacol Rev 1980; 32: 229–313.Google ScholarPubMed
Sibley, D.R., Creese, P. - Interactions of ergot alkaloids with anterior pituitary D-2 dopamine receptors. Mol Pharmacol 1983; 23: 585–593.Google ScholarPubMed
Sibley, D.R., De Lean, A., Creese, I. - Anterior pituitary dopamine receptors. Demonstration of interconvertible high and low affinity States of D-2 dopamine receptor. J Biol Chem 1982a; 257: 6351–6361.Google Scholar
Sibley, D.R., Leff, S.E., Creese, I. - Interactions of novel dopaminergic ligands with D-1 and D-2 dopamine receptors. Life Sci 1982b; 31: 637–645.CrossRefGoogle Scholar
Sokoloff, P., Brann, M., Redouane, K., Martres, M.P., Schwartz, J.C., Bouthenet, M.L., Sales, N., Mann, A., Hamdi, P., Wermuth, C.G., Roy, J., Morgat, J.L. - The use of 3H-(-) DO 710 as selective dopaminergic ligand lor binding and autoradiographic studies. Eur J Pharmacol 1985b; 107: 243–251.CrossRefGoogle Scholar
Sokoloff, P., Martres, M.P., Delandre, M., Redouane, K., Schwartz, J.C. - 3H-domperidone binding sites differ in rat striatum and pituitary. Naunyn Schmiedeberg's Arch Pharmacol 1984; 327: 221–227.CrossRefGoogle ScholarPubMed
Sokoloff, P., Martres, M.P., Schwartz, J.C. - Three classes of dopamine receptor (D-2, D-3, D-4) identifted by binding studies with 3H-apomorphine and 3H-domperidone. Naunyn-Schmiedeberg's Arch Pharmacol 1980; 315: 89–102.CrossRefGoogle ScholarPubMed
Sokoloff, P., Redouane, K., Brann, M., Martres, M.P., Schwartz, J.C. - 3H-DO 710 distinguishes guanine nucleotide sensitive and insensitive dopamine binding sites. Naunyn Schmiedeberg's Arch Pharmacol 1985a; 329: 236–243.CrossRefGoogle Scholar
Ungerstedt, U. - Behavioral Pharmacology reflecting catecholamine neurotransmission. In: Szekeres, L. ed.: Adrenergic activators and inhibitors, 449–519, Springer, Berlin, Heidelberg, New York, 1980.Google Scholar
Urba-Holmgren, R., Holmgren, B., Anias, J. - Preand postsynaptic dopaminergic receptors involved in apomorphineinduced yawning. Acta Neurobiol Exp 1982; 42: 115–125.Google Scholar
Vasse, M., Protais, P., Costentin, J., Schwartz, J.C. - Unexpected potentiation by discriminant benzamide derivatives of stereotyped behaviours elicited by dopamine agonists in mice. Naunyn Schmiedeberg's Arch Pharmacol 1985; 329: 108–116.CrossRefGoogle ScholarPubMed
Venter, J.C., Eddy, B., Hall, L.M., Fraser, C.M. - Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with alpha 1-adrenergic receptors. Proc Natl Acad Sci 1984a; 81: 272–276.CrossRefGoogle Scholar
Venter, J.C., Horne, P., Eddy, B., Greguski, R., Fraser, C.M. - Alpha 1- adrenergic receptor structure. Mol Pharmacol 1984b; 26: 196–205.Google Scholar
Yamada, K., Furukawa, T. - Direct evidence for involvement of dopaminergic inhibition and cholinergic activation in yawning. Psychopharmacology 1980; 67: 39–45.CrossRefGoogle ScholarPubMed
Zahniser, N.R., Molinoff, P.B. - Effect of guanine nucleotides on striatal dopamine receptors. Nature 1978; 275, 453-455.CrossRefGoogle ScholarPubMed
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