D2-Family Receptors in Schizophrenia: Distribution and Implications for Treatment

Lahti, Robert A.; Lahti, Adrienne C.; Tamminga, Carol A.; Ranhosky,; Kleber, HerbertD.; Wise, R.A.; Sethy,

doi:10.1097/00002826-199501001-00013

Clinical Neuropharmacology

1995

DOI: 10.1097/00002826-199501001-00013

|View full text |Cite

D2-Family Receptors in Schizophrenia: Distribution and Implications for Treatment

Robert A. Lahti

Adrienne C. Lahti

Carol A. Tamminga

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

1996

2005

Publication Types

Select...

Article5

Relationship

Self Cite0

Independent5

Authors

Journals

Cited by 5 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively, if normal D 2 occupancies are found for novel APDs, then the lower EPS propensity may be explained by additional effects on other targets that hinder the expression of EPS. Another point of great scientific interest is to gain knowledge on the association between antipsychotic activity and occupancies of Drlike receptors at extrastriatal sites that may be more important for antipsychotic activity, including areas where D 3 and D 4 receptors are expressed at higher levels (Lahti et al 1995a (Pilowsky et al 1997a). …”

mentioning

confidence: 99%

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

View full text Add to dashboard Cite

The pharmacological properties of the novel antipsychotic drugs (APDs) risperidone, sertindole, olanzapine, quetiapine, ziprasidone, remoxipride, and amperozide are reviewed and compared with haloperidol and clozapine. Focus is made on their receptor profiles, their effects in animal models used for evaluation of antipsychotic activity, and extrapyramidal side effects (EPS). In addition, the contrasting actions of these compounds on animal modelsDuring the last decade there has been a dramatic increase in the efforts to develop novel antipsychotic drugs (APDs) with improved clinical efficacy and fewer or no extrapyramidal side effects (EPS) than the classical APDs such as haloperidol and fluphenazine. These efforts were undoubtedly inspired by the previous development of clozapine, which fulfilled these criteria to a large extent, although having other troublesome side From the Pharmacological Research, H. Lundbeck A/S, Ohiliavej 9, DK-2500, Copenhagen-Valby, Denmark.Address correspondence to: J0rn Arnt, Pharmacological Research, H. Lundbeck A/5, Ottiliavej 9, DK-2500 Copenhagen-Valby, Denmark.Received January 6, 1997; revised June 26, 1997; accepted July 7, 1997. effects (Baldessarini and Frankenburg 1991; Coward 1992;Wagstaff and Bryson 1995;Buchanan 1995; Ashby and Wang 1996).The novel APDs were assigned the popular term "atypical antipsychotic" drugs to differentiate them from the classic or "typical" APDs or neuroleptics. The most widely accepted definition of a neuroleptic is a compound that has antipsychotic activity and induces EPS with high frequency. The definition of "a typicality" was equivocal, however, because the term was often used for drugs before any clinical results were available. For example, the term was applied to a compound that induced little or no catalepsy in rats, and that was effective in another model believed to reflect antipsychotic activity, e.g., inhibition of O-amphetamine (AMPH)-induced hypermotility. A more precise definition is to base it solely on clinical evidence as a wide differentiation between the dosages used to control psychosis and those inducing EPS-or on other aspects of clinical superior-0893-133X/98/$19.00 PI! 50893-133X(97)00112-7 64 J. Arnt and T. Skarsfeldt ity over classic APDs, e.g., efficacy on negative symptoms of schizophrenia or in drug-resistant patients (for recent review, see Kinan and Lieberman 1996). However, because these very different characteristics are difficult to incorporate in a common definition, we suggest that the terminology "atypical" is best avoided. Indeed, as will be discussed, novel APDs show many individual differences.The suggested alternative terminology "novel APO" is also not precise, but it can be defined as a compound that has been shown to inhibit positive symptoms of schizophrenia and has either been recently launched or is in phase II/III clinical development. Their specific profiles can be described more precisely, e.g., EPS-free APO, etc. It is not anticipated that novel APDs will be marketed in the future, unless hav...

show abstract

mentioning

confidence: 99%

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Arnt

Skarsfeldt

1998

Neuropsychopharmacology

681

443

View full text Add to dashboard Cite

show abstract

Evidence that D2 receptor-mediated activation of hypothalamic tuberoinfundibular dopaminergic neurons in the male rat occurs via inhibition of tonically active afferent dynorphinergic neurons11This work was presented in poster form at the 25th Annual Meeting of the Society for Neurosciences (San Diego, CA; November 1995).

et al. 1996

View full text Add to dashboard Cite

Associative and limbic regions of monkey striatum express high levels of dopamine D₃ receptors: effects of MPTP and dopamine agonist replacement therapies

Morissette¹,

Goulet²,

Grondin

et al. 1998

Eur J of Neuroscience

103

View full text Add to dashboard Cite

The role of the dopamine D3 receptor subtype in the central nervous system is still not well understood. It has a distinct and restricted distribution, mostly associated with limbic territories of the striatum (olfactory tubercle and the shell of nucleus accumbens) in rat brain. Dopaminergic denervation induced by a 6-hydroxydopamine lesion of the nigrostriatal system in rat down-regulates the expression of the D3 receptor. In the present study, we investigated the functional neuroanatomy of the dopamine D3 receptor subtype in the monkey (Macaca fascicularis) basal ganglia. We also studied the effect of administration of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and chronic D1-like (SKF 82958) or D2-like (cabergoline) agonist treatments on dopamine D3 receptor levels using receptor autoradiography. Our results clearly show that the distribution of D3 receptors in the monkey is more closely related to associative and limbic components of the striatum (caudate-putamen), as compared with its sensorimotor counterpart. Hence, D3 receptors may be more specifically involved in cognitive and motivational aspects of striatal functions, which are elaborated in prefrontal, temporal, parietal, cingulate and limbic cortices. Moreover, MPTP administration significantly decreased levels of D3 receptors and this effect was reversed or compensated by a chronic treatment with a D1-like, but not a D2-like, receptor agonist. The D3 receptor may represent an important target for adjunct or direct therapy designed to improve cognitive deficits observed in patients with Parkinson's disease, schizophrenia and other illnesses with frontal lobe cognitive disturbances.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

D2-Family Receptors in Schizophrenia: Distribution and Implications for Treatment

Cited by 5 publications

References 0 publications

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Associative and limbic regions of monkey striatum express high levels of dopamine D₃ receptors: effects of MPTP and dopamine agonist replacement therapies

Contact Info

Product

Resources

About

D2-Family Receptors in Schizophrenia: Distribution and Implications for Treatment

Cited by 5 publications

References 0 publications

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Do Novel Antipsychotics Have Similar Pharmacological Characteristics? A Review of the Evidence

Associative and limbic regions of monkey striatum express high levels of dopamine D3 receptors: effects of MPTP and dopamine agonist replacement therapies

Contact Info

Product

Resources

About

Associative and limbic regions of monkey striatum express high levels of dopamine D₃ receptors: effects of MPTP and dopamine agonist replacement therapies