Last update 01 Nov 2024

D4 receptor x 5-HT2 receptor

Last update 01 Nov 2024

Basic Info

Related Targets

D4 receptor5-HT2 receptor

Drugs associated with D4 receptor x 5-HT2 receptor

Fananserin

Target

5-HT2 receptor x D4 receptor

Mechanism

5-HT2 receptor antagonists [+1]

Active Org.

Rhone-Poulenc SA

Originator Org.

Sanofi

Active Indication-

Inactive Indication

Anxiety Disorders [+2]

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

1192U90

Target

5-HT1A receptor x 5-HT2 receptor x D2 receptor x D4 receptor

Mechanism

5-HT1A receptor agonists [+3]

Active Org.-

Originator Org.

GSK Plc

Active Indication-

Inactive Indication

Schizophrenia

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

U-96415E

Target

5-HT2 receptor x D4 receptor

Mechanism

5-HT2 receptor antagonists [+1]

Active Org.-

Originator Org.

Pharmacia Corp.

Active Indication-

Inactive Indication

Schizophrenia

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with D4 receptor x 5-HT2 receptor

100 Translational Medicine associated with D4 receptor x 5-HT2 receptor

0 Patents (Medical) associated with D4 receptor x 5-HT2 receptor

Literatures (Medical) associated with D4 receptor x 5-HT2 receptor

01 Jul 2008·The American Journal of Emergency MedicineQ4 · MEDICINE

Profound hypothermia secondary to normal ziprasidone use

Q4 · MEDICINE

Article

Author: Richard Paula ; David A. Wein ; Gregory M. Gibbons

Clinically significant hypothermia is a commonly evaluated condition in emergency medicine. Most cases are related to prolonged exposure to the environment, infection, or endocrinopathies. Presented here is a case of hypothermia likely induced by an atypical antipsychotic medication. A 69-year-old incarcerated man presented to our emergency department with an oral temperature of 85 degrees F (29.4 degrees C). The patient was taking ziprasidone (Geodon, Pfizer, New York, NY) 80 mg twice daily. Atypical antipsychotic medications have been implicated in numerous cases of clinically significant hypothermia. The mechanism of action for antipsychotics has not been fully elucidated, but the hypothermia induced by this class of medications is believed to be driven through the antagonism of the dopamine (D(1-4)) and 5-hydroxytryptamine-2 (5-HT2) receptors. It has been theorized that under normal conditions, there is a balance between dopamine acting to reduce the body temperature and 5-HT2 acting to elevate body temperature. Atypical antipsychotics, particularly ziprasidone, appear to have a higher affinity to antagonize the 5-HT2 receptor and less at the D(2) receptor, therefore creating an imbalance favoring the lowering of core body temperature. Other theories include the antagonism of alpha(1) receptors by these medications causing vasodilatation and shunting of blood to the skin causing profound heat loss. An antipsychotic medication can be the sole cause of hypothermia or it can be one of a number of possible causes coexisting in the individual with hypothermia.

01 Nov 1997·American Journal of PsychiatryQ1 · MEDICINE

PET Evidence That Loxapine Is an Equipotent Blocker of 5-HT₂ and D₂ Receptors: Implications for the Therapeutics of Schizophrenia

Q1 · MEDICINE

Article

Author: Kapur, S ; Zipursky, R ; Remington, G ; Houle, S ; McKay, G ; Jones, C

OBJECTIVELoxapine, a dibenzoxazepine antipsychotic, is closely related to clozapine and shares clozapine's high affinity for binding to serotonin 5-HT2 and dopamine D4 receptors. The purpose of this study was to document loxapine's 5-HT2 and D2 receptor occupancy in vivo in patients with psychoses.METHODTen patients who were taking loxapine (10-100 mg/day) had their D2 and 5-HT2 receptors assessed by means of positron emission tomography with [11C]raclopride and [18F]setoperone, respectively.RESULTSThe D2 receptor occupancy ranged from 43% to 90%; 5-HT2 occupancy varied from 27% to near saturation. Statistical comparison of the results showed that loxapine was equipotent in blocking 5-HT2 and D2 receptors.CONCLUSIONSLoxapine differs from typical neuroleptics in demonstrating a high degree of 5-HT2 receptor occupancy. However, it is not "atypical" like clozapine and risperidone, since its 5-HT2 occupancy is not higher than its D2 occupancy. The results demonstrate that a high level of 5-HT2 occupancy is not a sufficient condition for atypicality. If atypical antipsychotic action is predicated on a combination of 5-HT2 and D2 effects, then it requires > 80% 5-HT2 occupancy in conjunction with < 80% D2 occupancy.

01 Jul 1997·The Journal of pharmacology and experimental therapeutics

In vitro and in vivo characterization of the dopamine D4 receptor, serotonin 5-HT2A receptor and alpha-1 adrenoceptor antagonist (R)-(+)-2-amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl] pyrrolidin-3-yl]thiazole (NRA0045).

Article

Author: Kawashima, N ; Nakazato, A ; Ogawa, S ; Chaki, S ; Yoshikawa, R ; Okuyama, S ; Imagawa, Y ; Kumagai, T ; Tomisawa, K ; Ikeda, Y ; Nagamine, M ; Suzuki, Y

(R)-(+)-2-Amino-4-(4-fluorophenyl)-5-[1-[4-(4-fluorophenyl)-4-oxobutyl]+ ++pyrrolidin-3-yl]thiazole (NRA0045), a novel thiazole derivative, has high affinities for the human cloned dopamine D4.2, D4.4 and D4.7 receptors, with Ki values of 2.54, 0.55 and 0.54 nM, respectively. NRA0045 is approximately 91-fold more potent at the dopamine D4.2 receptor, compared with human cloned dopamine D2L receptor. NRA0045 also has high affinities for the serotonin (5-HT)2A receptor (Ki = 1.92 nM) and alpha-1 adrenoceptor (Ki = 1.40 nM) but weak affinities (IC50 values are approximately 1 microM) for six other neurotransmitter receptors (adenosine1, 5-HT1A, 5-HT1C, dopamine transporter, alpha2A and alpha2A) and negligible affinities (IC50 values are over 10(-5) M) for 42 other receptors, including neurotransmitters and hormones, ion channels and second messenger systems. Locomotor hyperactivity induced by methamphetamine (1 mg/kg i.p.) in mice was dose-dependently antagonized by NRA0045 (ED50 = 0.5 mg/kg i.p. and 1.9 mg/kg p.o., respectively). Methamphetamine (10 mg/kg i.p.)-induced stereotyped behavior in mice was dose-dependently antagonized by NRA0045, whereas NRA0045 did not exceed 50% inhibition even at the highest dose given (30 mg/kg i.p.). Catalepsy was dose-dependently and significantly induced by NRA0045 in rats, whereas NRA0045 did not exceed 50% induction even at the highest dose given (30 mg/kg i.p.). Thus NRA0045 blocks behaviors associated with activation of the mesolimbic/mesocortical dopaminergic neurons more selectively than behaviors associated with nigrostriatal dopaminergic neurons. In rats, tryptamine-induced clonic seizure, a 5-HT2 receptor-mediated behavior, was also dose-dependently inhibited by NRA0045 (ED50 = 1.7 mg/kg i.p.). Norepinephrine-induced lethality is regarded as being induced through the alpha-1 adrenoceptor. NRA0045 dose-dependently antagonized norepinephrine-induced lethality in rats (ED50 = 0.2 mg/kg i.p.). Thus NRA0045 may have a unique antipsychotic activity with regard to dopamine D4 and 5-HT2A receptors and alpha-1 adrenoceptor antagonistic activities, without producing the extrapyramidal side effects.

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