Inverse Agonists and Serotonergic Transmission From Recombinant, Human Serotonin (5-HT)1B Receptors to G-Protein Coupling and Function in Corticolimbic Structures in vivo

Millan, Mark J.; Gobert, Alain P.; Audinot, Valérie; Dekeyne, Anne; Newman‐Tancredi, Adrian

doi:10.1016/s0893-133x(99)00007-x

Cited by 10 publications

(2 citation statements)

References 35 publications

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“…Cascades from certain natural antidepressants such as hyperforin have also been observed (Bouron and Lorrain, 2014). (3) Any linear actuation of drugs may be nullified by «constitutionally active» receptors: those that show spontaneous linking to G proteins (Millan et al, 1999). These receptors act as «inverted agonists,» annulling the activity of agonists although the effects of both may be blocked again by «neutral» antagonists (Seifert and Wenzel-Seifert, 2002).…”

Section: Inherent Limits On the Effects Of Psychoactive Medicationmentioning

confidence: 99%

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

Campagne¹

2021

RPPC

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Improving the efficacy of depression treatment is a clinical necessity. «Synergy» is the systematic process in which different treatments of and approaches to mood disorders are evaluated and made to work coherently to optimize their results. Depression treatment has shown to benefit from the synergy of pharmacological and psychological processes. Our aim was to evaluate present evidence as to synergizing psychological therapy and pharmacotherapy in mood disorders, reflecting the related brain systems and circulating biological substances. Multiple brain regions are involved in mood disorders, resulting in multiple-target effects of substances, each influencing neurobiological balance, and depending on individual aspects. Large studies showed that psychological treatment may, overall, be more effective than medication. However, the synergy of both provided significantly increased effects that were largely independent of each other, and each added about 50% to the overall effects of combined treatment. Identified neuropsychobiological pathways were found, as well as appreciable evidence that, in depression, the synergy of both treatments can be expected to produce better results through reciprocal effects in cortical, subcortical and visceral systems. In compromised situations such as pregnancy and adolescence, psychological treatments for mood disorders may have preference over drug treatment, but synergy remains essential.

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Section: Inherent Limits On the Effects Of Psychoactive Medicationmentioning

confidence: 99%

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

Campagne¹

2021

RPPC

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“…5‐HT 1B receptors are involved in the control of mood, motor function and cognition, and 5‐HT 1B autoreceptors on serotonergic terminals modulate serotonin release (Engel et al ., 1986; Barnes & Sharp, 1999; Meneses, 1999; Millan et al ., 1999; Sari et al ., 1999). Consequently, an understanding of the mechanisms of signal transduction at 5‐HT 1B receptors is relevant to the etiology and treatment of affective, neurological and cardiovascular disorders and to the management of migraine.…”

Section: Introductionmentioning

confidence: 99%

h5‐HT_1B receptor‐mediated constitutive Gα_i3‐protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5‐HT

Newman‐Tancredi

Cussac

Marini

et al. 2003

British J Pharmacology

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1 Serotonin 5-HT 1B receptors couple to G-proteins of the Gi/o family. However, their activation of specific G-protein subtypes is poorly characterised. Using an innovative antibody capture/guanosine-5 0 -0-(3-[ 35 S]thio)-triphosphate ([ 35 S]GTPgS) binding strategy, we characterised Ga i3 subunit activation by h5-HT 1B receptors stably expressed in Chinese hamster ovary (CHO) cells. 2 The agonists, 5-HT, alniditan and BMS181,101, stimulated Ga i3 , whereas methiothepin and SB224,289 behaved as inverse agonists. The selective 5-HT 1B receptor ligand, S18127, modestly stimulated Ga i3 and reversed the actions of both 5-HT and methiothepin. S18127 (1 mm) also produced parallel, dextral shifts of the 5-HT and methiothepin isotherms. In contrast, at 10 mm NaCl, basal activity was enhanced and the inverse agonist activity of methiothepin was accentuated. Under these conditions, 5-HT decreased Ga i3 activation. 5 In conclusion, at h5-HT 1B receptors expressed in CHO cells: (i) inverse agonist induced inhibition of Ga i3 , and its reversal by S18127, reveals constitutive activation of this Ga subunit; (ii) constitutive Ga i3 activation can be quantified by isotopic dilution [ 35 S]GTPgS binding and (iii) decreasing NaCl concentrations enhances Ga i3 activation and leads to protean agonist properties of 5-HT: that is a switch to inhibition of Ga i3 .

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Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

Stenfors

Ross

2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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The possibility that 5-HT(1B) receptors display constitutive activity in vivo, i.e. have a basal agonist-independent activity, was examined in guinea-pigs depleted of endogenous brain 5-HT by pre-treatment with reserpine. Under these conditions (5 mg/kg s.c. reserpine 24 h before the experiment), hypothalamic 5-HT concentration was reduced by more than 97%. In reserpine-treated animals, 5-HT synthesis [measured as the accumulation of 5-hydroxytryptophan (5-HTP) after inhibition of the aromatic amino acid decarboxylase with m-hydroxybenzylhydrazine dihydrochloride (NSD 1015, 100 mg/kg s.c.)] was similar to that in non-treated guinea-pigs. The formation of 5-hydroxyindoleacetic acid (5-HIAA) was enhanced by reserpine treatment. The 5-HT(1B/1D) receptor agonist 3-( N-methylpyrrolidin-2- R-ylmethyl)-5-(3-nitropyrid-2-ylamino)-1 H-indole (CP-135,807) decreased 5-HT synthesis and 5-HIAA formation to the same extent in reserpine-treated and naive animals showing that the terminal 5-HT(1B) autoreceptors were functionally active during reserpine treatment. The 5-HT(1B) inverse agonist 1'-methyl-5-([2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl)-4-yl]carbonyl)-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4'-piperidine] hydrochloride (SB-224289, 4 mg/kg s.c.), which in naive guinea-pigs significantly enhanced 5-HIAA formation and tended to enhance 5-HT synthesis, had no effect in the reserpine-treated animals. Likewise, SB-224289 did not change the rectal temperature in reserpine-treated guinea-pigs although the agonist CP-135,807 had a significant hypothermic effect in these animals. It is concluded that no constitutive activity of 5-HT(1B) autoreceptors (5-HIAA formation) or 5-HT(1B) heteroreceptors (rectal temperature) could be detected under the in vivo experimental conditions used.

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Inverse Agonists and Serotonergic Transmission From Recombinant, Human Serotonin (5-HT)1B Receptors to G-Protein Coupling and Function in Corticolimbic Structures in vivo

Cited by 10 publications

References 35 publications

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

h5‐HT_1B receptor‐mediated constitutive Gα_i3‐protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5‐HT

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

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Inverse Agonists and Serotonergic Transmission From Recombinant, Human Serotonin (5-HT)1B Receptors to G-Protein Coupling and Function in Corticolimbic Structures in vivo

Cited by 10 publications

References 35 publications

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

Antidepressants and Psychological Treatment: Hard Reasons for Synergy

h5‐HT1B receptor‐mediated constitutive Gαi3‐protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5‐HT

Failure to detect in vivo inverse agonism of the 5-HT 1B receptor antagonist SB-224289 in 5-HT-depleted guinea-pigs

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h5‐HT_1B receptor‐mediated constitutive Gα_i3‐protein activation in stably transfected Chinese hamster ovary cells: an antibody capture assay reveals protean efficacy of 5‐HT