Effects of local application of 5-hydroxytryptamine into the dorsal or median raphe nuclei on haloperidol-induced catalepsy in the rat

Wadenberg, Marie Louise; Young, Kimball; Richter, J.; Hicks, Paul B.

doi:10.1016/s0028-3908(98)00162-2

Cited by 31 publications

(18 citation statements)

References 26 publications

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“…1,[3][4][5] Several studies demonstrated that activation of 5-HT 1A receptors improves antipsychotic-induced EPS and motor disabilities in animal models of Parkinson's disease. [10][11][12][13][14][15][16] In our studies, 5-HT 1A agonists (e.g., 8-hydroxy-2-(di-n-propylamino)-tetralin and tandospirone) ameliorated haloperidol-induced bradykinesia and catalepsy with potencies similar to those of antiparkisonian agents (e.g., trihexyphenidyl and L-3,4-dihydroxyphenylalanine (L-DOPA)). 13,14) Consistently with these anti-EPS actions, 5-HT 1A agonists reversed striatal Fos protein expression induced by haloperidol, indicating that 5-HT 1A receptors counteract D 2 receptor blockade by antipsychotics in the striatum.…”

Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 55%

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno

Shimizu

Tokudome

2013

Biological & Pharmaceutical Bulletin

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The serotonergic nervous system plays crucial roles in regulating psycho-emotional, cognitive, sensorimotor and autonomic functions. It is now known that multiple serotonin (5-hydroxytryptamine; 5-HT) receptors regulate extrapyramidal motor functions, which are implicated in pathogenesis and/or treatment of various neurological disorders (e.g., Parkinson's disease and drug-induced extrapyramidal motor deficits).

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Section: Roles Of 5-ht Receptors In Modulating Extrapyramidal Motor Dmentioning

confidence: 55%

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Ohno

Shimizu

Tokudome

2013

Biological & Pharmaceutical Bulletin

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“…A combination of serotonin 5-HT 1A agonism and D 2 antagonism may confer positive benefits for the treatment of schizophrenia (see for reviews Millan, 2000;Meltzer et al, 2003). One such mechanism would be by the reduction of neurological or EPS side effects seen in preclinical (Prinssen et al, 1999(Prinssen et al, , 2000Wadenberg and Ahlenius, 1991;Wadenberg, 1996;Wadenberg et al, 1999;Christoffersen and Meltzer, 1998; and see Depoortere et al, 2003) and clinical studies (Goff et al, 1991;Yoshida et al, 1998). In the rat, the reduction of the cataleptic effect was only evident with moderate to high intrinsic activity 5-HT 1A receptor agonists (Prinssen et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

“…For example, in the conditioned avoidance response (CAR) model of schizophrenia the nonselective 5-HT 1A agonist (7)-8-hydroxy (di-n-aminopropylamino) tetralin (8-OH-DPAT) not only induced CAR disruption but enhanced the effects of the dopamine D 2 receptor antagonists haloperidol and raclopride (Wadenberg and Ahlenius, 1991;Prinssen et al, 1996). Rather than increasing EPS the 5-HT 1A agonists 8-OHDPAT and ipsapirone reduced EPS-like symptoms in rodents and non-human primates (Prinssen et al, 1999(Prinssen et al, , 2000Wadenberg and Ahlenius, 1991;Wadenberg, 1996;Wadenberg et al, 1999;Christoffersen and Meltzer, 1998). These preclinical studies are supported by the finding that buspirone and tandospirone attenuated Parkinsonian-like signs and tardive dyskinesia seen in schizophrenics (Goff et al, 1991;Yoshida et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

SLV313 (1-(2,3-Dihydro-Benzo[1,4]Dioxin-5-yl)-4- [5-(4-Fluoro-Phenyl)-Pyridin-3-ylmethyl]-Piperazine Monohydrochloride): A Novel Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist Potential Antipsychotic Drug

McCreary

Glennon

Ashby

et al. 2006

Neuropsychopharmacol

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Combined dopamine D 2 receptor antagonism and serotonin (5-HT) 1A receptor agonism may improve efficacy and alleviate some side effects associated with classical antipsychotics. The present study describes the in vitro and in vivo characterization of 1-(2,3-dihydrobenzo[1,4]dioxin-5-yl)-4-[5-(4-fluoro-phenyl)-pyridin-3-ylmethyl]-piperazine monohydrochloride (SLV313), a D 2/3 antagonist and 5-HT 1A agonist. SLV313 possessed high affinity at human recombinant D 2 , D 3 , D 4 , 5-HT 2B , and 5-HT 1A receptors, moderate affinity at 5-HT 7 and weak affinity at 5-HT 2A receptors, with little-no affinity at 5-HT 4 , 5-HT 6 , a 1 , and a 2 (rat), H 1 (guinea pig), M 1 , M 4 , 5-HT 3 receptors, and the 5-HT transporter. SLV313 had full agonist activity at cloned h5-HT 1A receptors (pEC 50 ¼ 9.0) and full antagonist activity at hD 2 (pA 2 ¼ 9.3) and hD 3 (pA 2 ¼ 8.9) receptors. In vivo, SLV313 antagonized apomorphine-induced climbing and induced 5-HT 1A syndrome behaviors and hypothermia, the latter behaviors being antagonized by the 5-HT 1A antagonist WAY100635. In a drug discrimination procedure SLV313 induced full generalization to the training drug flesinoxan and was also antagonized by WAY100635. In the nucleus accumbens SLV313 reduced extracellular 5-HT and increased dopamine levels in the same dose range. Acetylcholine and dopamine were elevated in the hippocampus and mPFCx, the latter antagonized by WAY100635, suggesting possible 5-HT 1A -dependent efficacy for the treatment of cognitive and attentional processes. SLV313 did not possess cataleptogenic potential (up to 60 mg/kg p.o.). The number of spontaneously active dopamine cells in the ventral tegmental area was reduced by SLV313 and clozapine, while no such changes were seen in the substantia nigra zona compacta following chronic administration. These results suggest that SLV313 is a full 5-HT 1A receptor agonist and full D 2/3 receptor antagonist possessing characteristics of an atypical antipsychotic, representing a potential novel treatment for schizophrenia. Neuropsychopharmacology (2007) 32, 78-94.

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“…Second, numerous laboratories have demonstrated anticataleptic properties of 5-HT 1A agonists in rodents, indicating that activation of 5-HT 1A receptors should reduce EPS induced by D 2 receptor blockade (Invernizzi et al 1988;McMillen et al 1988;Wadenberg et al 1999). The extent to which 5-HT 1A agonists are able to reverse neurolepticinduced catalepsy is dependent on the level of efficacy of the ligand: relatively high efficacy activation, for example by the prototypical agonist, 8-OH-DPAT, is necessary to completely abolish neuroleptic-induced catalepsy (Kleven et al , 2005Prinssen et al 2002Prinssen et al , 1996.…”

Section: Introductionmentioning

confidence: 99%

Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties

Newman‐Tancredi

Kleven²

2011

Psychopharmacology

145

108

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Recent compounds exhibiting combined 5-HT(1A)/D(2) properties may be effective in treating a broader range of symptoms of schizophrenia and be better tolerated than existing antipsychotics. Nevertheless, further investigations are necessary to evaluate recent compounds, notably in view of their differing levels of 5-HT(1A) affinity and efficacy, which can markedly influence activity and side-effect profiles.

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Effects of local application of 5-hydroxytryptamine into the dorsal or median raphe nuclei on haloperidol-induced catalepsy in the rat

Cited by 31 publications

References 26 publications

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

Pathophysiological Roles of Serotonergic System in Regulating Extrapyramidal Motor Functions

SLV313 (1-(2,3-Dihydro-Benzo[1,4]Dioxin-5-yl)-4- [5-(4-Fluoro-Phenyl)-Pyridin-3-ylmethyl]-Piperazine Monohydrochloride): A Novel Dopamine D2 Receptor Antagonist and 5-HT1A Receptor Agonist Potential Antipsychotic Drug

Comparative pharmacology of antipsychotics possessing combined dopamine D2 and serotonin 5-HT1A receptor properties

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