Kegg Pathway: Butyrophenones

KEGG ID: 07031

Reference Diagram

KEGG Diagram for Butyrophenones

Rat

There are 0 IPI Records from this pathway found in Rattus norvegicus.

Location of Butyrophenones proteins on Rat Genome

IPI Record Position

Mouse

There are 0 IPI Records from this pathway found in Mus musculus.

Location of Butyrophenones proteins on Mouse Genome

IPI Record Position

Human

There are 0 IPI Records from this pathway found in Homo sapiens.

Location of Butyrophenones proteins on Human Genome

IPI Record Position

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Recent Literature

[Olanzapine versus haloperidol: effectiveness in functionality and health state in a sample of Venezuelan patients with schizophrenia]

Vertex. 2008 Sep-Oct; 19(81): 254-60
Adrianzén C, Sánchez M, Córdova J, Castillo I

OBJECTIVE: To compare olanzapine versus haloperidol effectiveness, in terms of relapse rates in Venezuelan patients with schizophrenia. METHODS: A randomized, open label, follow-up study of 9-months after clinical stabilization or hospital discharged was conducted. The Medical Outcomes Study Form Health Survey (SF-36) and the Quality of Life Index from Mezzic & Cohen were used to evaluate the health state and quality of life. Safety parameters were collected. RESULTS: Thirty-one patients in olanzapine and 40 in haloperidol were enrolled and discontinuation rates were 65% and 68% respectively. Only one patient in haloperidol relapsed. Health status improved more with olanzapine showing statistically significant improvement in five of the eight items of the SF-36. Olanzapine was slightly superior improving quality of life. More adverse events were registered with haloperidol (p = 0.036). More extrapyramidal symptoms, akathisia and insomnia were reported with haloperidol and more weight gain with olanzapine but the differences were not significant. CONCLUSIONS: Both medications were similar preventing relapses. Health status and functionality improved more with olanzapine versus haloperidol. Safety results are consistent with the known profile of the drug. Study limitations on design and conduction of this study restrict its generalization.

Droperidol: past, present and future.

Anaesthesia. 2009 Nov; 64(11): 1161-4
Sneyd JR

GPR37 surface expression enhancement via N-terminal truncation or protein-protein interactions.

Biochemistry. 2009 Nov 3; 48(43): 10286-97
Dunham JH, Meyer RC, Garcia EL, Hall RA

GPR37, also known as the parkin-associated endothelin-like receptor (Pael-R), is an orphan G-protein-coupled receptor (GPCR) that exhibits poor plasma membrane expression when expressed in most cell types. We sought to find ways to enhance GPR37 trafficking to the cell surface to facilitate studies of GPR37 functional activity in heterologous cells. In truncation studies, we found that removing the GPR37 N-terminus (NT) dramatically enhanced the receptor's plasma membrane insertion. Further studies on sequential NT truncations revealed that removal of the first 210 amino acids increased the level of surface expression nearly as much as removal of the entire NT. In studies examining the effects of coexpression of GPR37 with a variety of other GPCRs, we observed significant increases in the level of GPR37 surface expression when the receptor was coexpressed with adenosine receptor A(2A)R or dopamine receptor D(2)R. Co-immunoprecipitation experiments revealed that full-length GPR37 and, to a greater extent, the truncated GPR37 were capable of robustly associating with D(2)R, resulting in modestly altered D(2)R affinity for both agonists and antagonists. In studies examining potential interactions of GPR37 with PDZ scaffolds, we observed a specific interaction between GPR37 and syntenin-1, which resulted in a dramatic increase in the level of GPR37 surface expression in HEK-293 cells. These findings reveal three independent approaches (N-terminal truncation, coexpression with other receptors, and coexpression with syntenin-1) by which GPR37 surface trafficking in heterologous cells can be greatly enhanced to facilitate functional studies with this orphan receptor.

Chorea associated with gabapentin use in an elderly man.

Am J Geriatr Pharmacother. 2009 Aug; 7(4): 220-4
Attupurath R, Aziz R, Wollman D, Muralee S, Tampi RR

BACKGROUND: Chorea is a hyperkinetic movement disorder characterized by irregular, flowing, nonstereotyped, random, involuntary movements. Huntington disease (HD) and drug-induced chorea account for >50% of adult-onset cases. Chorea associated with gabapentin, an anticonvulsant, has not been well documented. OBJECTIVE: The purpose of this article was to report a case of chorea that developed in an elderly man being treated with gabapentin for severe anxiety. CASE SUMMARY: A 75-year-old white man (height, 165.1 cm; weight, 65.8 kg; body mass index, 19.6 kg/m2) with anxiety disorder not otherwise specified was admitted to a geriatric medicine psychiatric unit in Connecticut because of worsening symptoms of anxiety affecting his cognitive ability. On evaluation, the patient had choreiform movements involving the neck, trunk, upper and lower extremities, and tongue. The patient reported that symptoms began after taking gabapentin 300 mg PO TID (prescribed by his geriatrician) for the treatment of anxiety. The patient had been taking gabapentin for >1 month when the symptoms first appeared. There was no known family history of HD, and patient workup was unremarkable for other conditions (eg, vascular disease of the brain, progressive dementia, infectious and metabolic disorders) that might present with chorea. The chorea lasted for ~4 months and resolved within 2 days after gabapentin discontinuation. CONCLUSION: This article reports a case of chorea in an elderly patient who was receiving gabapentin for the treatment of anxiety. After gabapentin discontinuation, the chorea resolved completely, indicating a probable adverse drug reaction.

[Complex therapy of schizophrenia]

Neuropsychopharmacol Hung. 2009 Mar; 11(1): 41-5
Gaszner P

Schizoprenia is not a consistent illness, but the symptoms free state do may achive with different methods. During the last fifty years the clinical psychopharmacology improved very quickly, but the psychotherapy and sociotherapy as well. The complex therapy of schizophrenia is a new method: the psychopharmacons together with psychotherapy (first of all with cognitive one), sociotherapy and psychiatric rehabilitation. During the acute or chronic phase of schizophrenia the psychopharmacons are the first line treatment, but the complex therapy is better. In the last forty years we tested this new therapy, finally conducted a clinical trial: with one psychopharmacon (monotherapy), with two or three psychopharmacons (combination) and with the complex therapy (one psychopharmacon together with psychotherapy, sociotherapy and psychiatric rehabilitation). The antipsychotics, first of all the second generations have a very good efficacy. Risperidone is proven to be an efficient product. Fields of indication: first psychotic episode, acut schizophrenic exacerbation, chronic schizophrenia, the treatment of behavior disorder in dementia, maniac phase of bipolar disorder, treatment of behavioral disorders.

[Delirium in the light of the most recent guidelines]

Przegl Lek. 2009; 66(4): 187-91
Klich-Raczka A, Piotrowicz K, Grodzicki T

The article presents the clinical picture of delirium characterized with acute, fluctuating altered levels of consciousness, inattention and cognitive function disorders. The article is comprised the most popular assessment scales for detecting (CAM - Confusion Assessment Method) and monitoring the course of delirium (DRS-R-98: Delirium Rating Scale-Revised-98; DOM: Delirium-O-Meter). The scales mentioned above contain unequivocally defined rating criteria of the patient's clinical state. The article mentions scientific studies concerning predisposing and precipitating factors for delirium such as age, severity of illnesses, cognitive impairment, metabolic and electrolyte disturbances, grouped according to the recommendation grades based on scientific evidence and the opinion of experts. Categories of recommendation of possible therapeutic intervention are presented with special emphasis being put on interventions that are always beneficial, useful, successful and safe. Moreover, recommendable pharmacological treatment methods (haloperidol, new antipsychotic drugs) as well as non-pharmacological ones (comprising routine screening of cognitive functions, comprehensive medical and nursing care) are described.

Effects of antipsychotic drugs on MK-801-induced attentional and motivational deficits in rats.

Neuropharmacology. 2009 Mar; 56(4): 788-97
Paine TA, Carlezon WA

BACKGROUND: Attentional deficits that accompany schizophrenia are not effectively treated by available antipsychotic medications. Disruption of NMDA receptor function is often used to model aspects of this disorder in rodents. We used the 5-choice serial reaction time task (5CSRTT) to characterize attentional deficits caused by acute administration or withdrawal from chronic administration of the NMDA receptor antagonist MK-801, and determine if they are ameliorated by haloperidol or clozapine. METHODS: Acute studies involved tests in the presence of MK-801: rats were administered haloperidol (0.008-0.125 mg/kg, SC) or clozapine (0.16-2.5 mg/kg, SC) in combination with MK-801 (0.25 mg/kg, IP) prior to daily test sessions. Chronic studies involved tests in the absence of MK-801: following daily tests, rats were administered MK-801 (0.5 mg/kg, IP) and tested 24 h later in the absence or presence of haloperidol or clozapine. RESULTS: Acute MK-801 disrupted performance: it decreased accuracy while increasing omissions, premature responses, and magazine entries. Haloperidol reduced disruptive effects associated with increased activation, whereas it exacerbated other deficits. Clozapine dose-dependently attenuated several of the MK-801-induced performance deficits. Withdrawal from chronic MK-801 progressively increased omissions and response latencies and decreased premature responding, suggesting an amotivational state. Neither haloperidol nor clozapine ameliorated these performance deficits. DISCUSSION: Acute administration and withdrawal from chronic MK-801 administration produced distinct behavioral profiles in the 5CSRTT. Acute MK-801 impaired attention and impulse control whereas chronic MK-801 withdrawal caused signs consistent with amotivation. Haloperidol and clozapine were more effective at attenuating deficits caused by acute MK-801 administration.

Neocortical movement representations are reduced and reorganized following bilateral intrastriatal 6-hydroxydopamine infusion and dopamine type-2 receptor antagonism.

Exp Neurol. 2009 Nov; 220(1): 162-70
Brown AR, Hu B, Antle MC, Teskey GC

The neurophysiologic model of Parkinson's disease predicts nigrostriatal dopamine depletion leads to increased inhibitory basal ganglia output resulting in frontal neocortical hypoactivity. The nature of this hypoactivation is not well understood and modeled predominantly by a unilateral representation. Intracortical microstimulation (ICMS) was used to probe topographic movement representations of the left forelimb motor area 2 weeks following sham, unilateral left hemisphere or bilateral intrastriatal 6-hydroxydopamine (6-OHDA) infusion and under acute dopamine receptor antagonism with haloperidol in non-lesioned rats. 6-OHDA infusions induced a significant loss of substantia nigra pars compacta (SNc) dopamine neurons. Bilateral SNc lesions and haloperidol significantly reduced map area which was preserved in unilateral lesions. All lesion conditions and haloperidol induced significant map reorganization, characterized by increased representation of distal forelimb movements. Results suggest basal ganglia dopamine deficiency can affect the topographic organization of sensorimotor neocortex and lead to significant reduction in the size of motor representations. We conclude that the neurophysiologic model is supported but that bilateral loss of dopamine is required to see a reduction in the size of motor maps.

In vivo evidence that constitutive activity of serotonin2C receptors in the medial prefrontal cortex participates in the control of dopamine release in the rat nucleus accumbens: differential effects of inverse agonist versus antagonist.

J Neurochem. 2009 Oct; 111(2): 614-23
Leggio GM, Cathala A, Neny M, Rouge-Pont F, Drago F, Piazza PV, Spampinato U

Control of the mesoaccumbens dopamine (DA) pathway by central serotonin(2C) receptors (5-HT(2C)Rs) involves different 5-HT(2C)R populations located within multiple brain areas. Here, using in vivo microdialysis in halothane-anesthetized rats, we assessed the role of medial prefrontal cortex (mPFC) 5-HT(2C)Rs in the control of basal and activated accumbal DA outflow, to identify the modalities of their recruitment and the role of 5-HT(2C)R constitutive activity. Intra-mPFC injection of the 5-HT(2C)R inverse agonist SB 206553 (0.5 microg/0.2 microL), without effect by itself, decreased accumbal DA outflow induced by morphine (2.5-10 mg/kg, s.c.), haloperidol (0.01 mg/kg, s.c.) or GBR 12909 (2.5 mg/kg, i.p.). Conversely, intra-mPFC injection of the 5-HT(2C)R antagonist SB 242084 (0.5 microg/0.2 microL), without effect by itself, decreased the effect of 10 mg/kg morphine, the only drug enhancing basal 5-HT outflow in the mPFC. The inhibitory effect of SB 206553 on 2.5 mg/kg morphine-stimulated DA outflow was suppressed by the concomitant intra-mPFC injection of SB 242084. Finally, changes of basal DA outflow induced by the 5-HT(2C)R agonist Ro 60-0175 (3 mg/kg, i.p.) or SB 206553 (5 mg/kg, i.p.) were unaffected by intra-mPFC injection of SB 242084. These results, showing that 5-HT(2C)R antagonist and inverse agonist behave differently in vivo, demonstrate that mPFC 5-HT(2C)Rs facilitate activated accumbal DA outflow and that 5-HT(2C)R constitutive activity participates in this interaction.

Validation of derivative spectrophotometry method for determination of active ingredients from neuroleptics in pharmaceutical preparations.

Acta Pol Pharm. 2009 Jul-Aug; 66(4): 351-6
Stolarczyk M, Apola A, Krzek J, Sajdak A

First (DI) and second (D2) order derivative spectrophotometric method with an application of base line to peak technique was used for determination of active pharmaceutical ingredients (API) at two wavelengths: fluphenazine (D1 at lambda = 251 nm and lambda = 265 nm, D2 at lambda = 246 nm and lambda = 269 nm), pernazine (D1 at lambda = 246 nm and lambda = 258 nm, D2 at lambda = 254 nm and lambda = 262 nm), haloperidol (DI at = 235 nm and lambda = 253 nm, D2 at lambda = 230 nm and lambda = 246 nm), and promazine (D1 at lambda = 246 nm and lambda = 251 nm, D2 at lambda = 255 nm and lambda = 262 nm). Linear dependence of derivative values on analyte concentration is maintained in a range 3.12 microg x mL(-1) - 44.80 microg x mL(-1). Detection and determination limits are in the range 0.51 - 3.23 microg x mL(-1) and 1.27 microg x mL(-1) - 9.80 microg x mL(-1), respectively. Determination results of drug constituents are very accurate. Recovery percentage is in a range 95.50% - 103.60%.

Obsessive-compulsive symptoms and disorder in patients with schizophrenia treated with clozapine or haloperidol.

Compr Psychiatry. 2009 Sep-Oct; 50(5): 437-42
Sa AR, Hounie AG, Sampaio AS, Arrais J, Miguel EC, Elkis H

We conducted a cross-sectional study to compare the prevalence and severity of obsessive-compulsive symptoms (OCSs) and obsessive-compulsive disorder (OCD) in patients with schizophrenia treated with clozapine or haloperidol. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I disorders-patient edition was used to diagnose schizophrenia and OCD. Sixty subjects, 40 of them using clozapine and 20 using haloperidol, completed the Yale-Brown Obsessive-Compulsive Scale, the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impression. The prevalence of OCD in patients taking clozapine was 20%, whereas the prevalence of patients taking haloperidol was 10%, although this difference was not statistically significant (P = .540). However, patients using clozapine showed higher severity of OCSs than patients using haloperidol (P = .027) did. When schizophrenia patients were divided according to the presence or absence of OCD or OCSs, patients with schizophrenia and OCD or OCSs showed higher severity of schizophrenia symptoms when compared to those with schizophrenia without OCD and OCSs (P = .002). A PANSS total score higher than 70 and the use of antidepressants were predictors of the presence of OCSs or OCD. Schizophrenia patients taking clozapine had higher severity scores both in obsessive-compulsive and schizophrenia rating scales. These results may support an association between the exacerbation of obsessive-compulsive phenomena and the use of clozapine.

A liquid chromatography-electrospray ionization-tandem mass spectrometry method for quantitation of aripiprazole in human plasma.

J Anal Toxicol. 2009 Jun; 33(5): 237-42
Lin SN, Lamm L, Newton TF, Reid MS, Moody DE, Foltz R

A rugged liquid chromatographic-electrospray ionization-tandem mass spectrometric (LC-ESI-MS-MS) method was developed and validated for accurate monitoring of steady-state plasma aripiprazole. Haloperidol-d(4) was chosen as the internal standard. ESI of aripiprazole and haloperidol-d(4) yielded abundant MH(+) ions, m/z 448 and 379, respectively. These ions were collision-dissociated to respective product ions of m/z 285 and 168. Ion-suppression experiments with blank plasma extracts showed substantial depressions of the product ions at retention times between 0.5 to 2 min, prohibiting development of a high-throughput LC-MS-MS method. A steep-gradient elution LC permitted a robust LC-ESI-MS-MS method with a 12-min analysis time. Aripiprazole was quantified from 0.2-mL aliquots of human plasma with acceptable precision and accuracy down to a lower limit of quantitation of 2 ng/mL. Aripiprazole was stable in plasma samples stored at room temperature for 24 h or exposed to three freeze-thaw cycles and in processed extracts stored at -20 degrees C for six days or on the autosampler at 10 degrees C for four days. The method has been successfully used for determinations of steady-state concentrations of aripiprazole in human subjects given daily oral doses of 15 mg. All measured concentrations were well within the quantitative range of 2 to 400 ng/mL.

Examination of reinforcement magnitude on the pharmacological disruption of fixed-ratio performance.

Exp Clin Psychopharmacol. 2009 Aug; 17(4): 237-46
Pinkston JW, Ginsburg BC, Lamb RJ

Behavioral momentum theory proposes that operant behavior is the product of two separable processes: its rate of occurrence and its resistance to change. Generally speaking, operant situations providing more densely spaced or greater magnitudes of reinforcement should be more resistant to disruption. Attempts to disrupt ongoing behavior by manipulating the availability of food or deprivation level typically have supported the predictions of behavioral momentum. Tests with pharmacological disruptors, however, have yielded mixed results. Most investigations of pharmacological disruption of operant behavior have evaluated momentum across situations that differ in rate of reinforcement. The present experiment was an attempt to systematically replicate prior work, but under conditions of differing reinforcement magnitudes. Pigeons were trained to key peck on a multiple fixed-ratio 30 schedule of food presentation, where different components programmed 2-, 4-, or 8-s access to grain. Resistance to rate-decreasing effects of drugs was evaluated with several compounds drawn from distinct pharmacological classes: chlordiazepoxide, cocaine, clonidine, haloperidol, morphine, and ethanol were tested. Additionally, disruption by prefeeding and extinction was examined. Generally, resistance to change by drug administration was not modulated by reinforcement magnitude. Prefeeding and extinction tests, however, replicated previous work, indicating that our procedure was sensitive to more common disruptors. The results give additional support to the notion that pharmacological disruptors may not behave in the manner predicted by behavioral momentum theory.

[Efficacy of clonidine transdermal patch for treatment of Tourette's syndrome in children]

Zhongguo Dang Dai Er Ke Za Zhi. 2009 Jul; 11(7): 537-9
Kang H, Zhang YF, Jiao FY, Guo XY, Gao XM

OBJECTIVE: Children with Tourette's syndrome (TS) have a poor treatment compliance due to side effects and inconvenient administration of oral drugs. This study explored the efficacy and safety of clonidine transdermal patch for treating TS in children. METHODS: A total of 119 children with TS were randomly treated with the clonidine transdermal patch (n=65) or with oral haloperidol (n=54). The therapeutic efficacy was assessed based on the results of the Yale Global Tic Severity Scale (YGTSS) 4 weeks after treatment. RESULTS: The clonidine transdermal patch group showed a higher reduction in the overall tic symptom scores (61.5+/-7.5%) than that in the haloperidol group (41.0+/-6.3%; p<0.05). Clonidine transdermal patch treatment was effective in 53 patients (81.5%) and 36 patients (67.5%) showed effective to oral haloperidol (p>0.05). Mild side effects (decrease of blood pressure and dizziness) were observed in 1 patient in the clonidine transdermal patch group. Mild hypermyotonia, drowsiness or lassitude as side effects occurred in 6 patients in the haloperidol group. CONCLUSIONS: Clonidine transdermal patch is effective for the treatment of TS in children and its side effects are mild and rare.

Long-term ventilatory adaptation and ventilatory response to hypoxia in plateau pika (Ochotona curzoniae): role of nNOS and dopamine.

Am J Physiol Regul Integr Comp Physiol. 2009 Oct; 297(4): R978-87
Pichon A, Zhenzhong B, Favret F, Jin G, Shufeng H, Marchant D, Richalet JP, Ge RL

We assessed ventilatory patterns and ventilatory responses to hypoxia (HVR) in high-altitude (HA) plateau pikas, repetitively exposed to hypoxic burrows, and control rats. We evaluated the role of neuronal nitric oxide synthase (nNOS) and dopamine by using S-methyl-l-thiocitrulline (SMTC) inhibitor and haloperidol antagonist, respectively. Ventilation (Vi) was measured using a whole body plethysmograph in conscious pikas (n = 9) and low-altitude (LA) rats (n = 7) at different Pi(O(2)) (56, 80, 111, 150, and 186 mmHg) and in HA acclimatized rats (n = 9, 8 days at 4,600 m) at two different Pi(O(2)) (56 and 80 mmHg). The effects of NaCl, SMTC, and haloperidol on ventilatory patterns were assessed in pikas at Pi(O(2)) = 56 and 80 mmHg. We observed a main species effect with larger Vi, tidal volume (VT), inspiratory time/total time (T(i)/T(tot)), and a lower expiratory time in pikas than in LA rats. Pikas had also a larger VT and lower respiratory frequency compared with HA rats in hypoxia. HVR of pikas and rats were not statistically different. In pikas, SMTC induced a significant increase in Vi and VT for a Pi(O(2)) of 56 mmHg, but had no effect for a PiO(2) of 80 mmHg, i.e., the living altitude of pikas. In pikas, haloperidol injection had no effect on any ventilatory parameter. Long-term ventilatory adaptation in pikas is mainly due to an improvement in respiratory pattern (VT and T(i)/T(tot)) with no significant improvement in HVR. The sensitivity to severe acute hypoxia in pikas seems to be regulated by a peripheral nNOS mechanism.

Intramuscular haloperidol versus intramuscular olanzapine for treatment of acute agitation: a cost-minimization study.

Pharmacotherapy. 2009 Aug; 29(8): 930-6
Freeman DJ, DiPaula BA, Love RC

STUDY OBJECTIVES: To investigate prescribing patterns for antipsychotic regimens based on intramuscular haloperidol or intramuscular olanzapine for treating acute agitation; to compare the costs of each drug regimen, which included adjunctive anxiolytics and/or anticholinergics; and to compare the effectiveness and safety of each drug regimen. DESIGN: Retrospective medical record review. SETTING: State psychiatric facility. PATIENTS: Twenty-seven patients who received intramuscular haloperidol to treat 47 episodes of acute agitation and 26 patients who received intramuscular olanzapine to treat 38 episodes. MEASUREMENTS AND MAIN RESULTS: Data from patients receiving the antipsychotic regimens between August 2004 and March 2007 were reviewed. Mean +/- SD doses were 6.4 +/- 2.4 mg (range 2.5-10 mg) for haloperidol and 8.1 +/- 2.3 mg (range 5-10 mg) for olanzapine. The mean +/- SD cost of treating an episode of agitation with haloperidol was significantly lower at $4.06 +/- 3.98 (range $1.74-18.35) versus $27.84 +/- 10.40 (range $21.58-52.46) for olanzapine (p<0.0001). Significantly fewer patients who received haloperidol than patients who received olanzapine required additional pharmacotherapy to manage agitation (41% vs 69%, chi(2)=4.34, p=0.04). No significant differences were found between groups in the mean number of repeat doses of psychotropic drugs needed/episode (0.6 [range 0-5] for haloperidol vs 0.8 [range 0-3] for olanzapine, p=0.47), in the percentages of patients who required seclusion and/or restraints (59% for haloperidol vs 58% for olanzapine, chi(2)=0.01, p=0.91), or in time spent in seclusion and/or restraints (3.7 +/- 7.1 for haloperidol vs 3.6 +/- 6.5 hrs for olanzapine, p=0.92). No adverse events were documented with either drug. CONCLUSION: For the treatment of acute episodes of agitation, regimens based on intramuscular haloperidol were significantly less expensive than and at least as effective as those based on intramuscular olanzapine.

Dopamine D2, D3, and D4 selective phenylpiperazines as molecular probes to explore the origins of subtype specific receptor binding.

J Med Chem. 2009 Aug 13; 52(15): 4923-35
Ehrlich K, Götz A, Bollinger S, Tschammer N, Bettinetti L, Härterich S, Hübner H, Lanig H, Gmeiner P

Assembling phenylpiperazines with 7a-azaindole via different spacer elements, we developed subtype selective dopamine receptor ligands of types 1a,c, 2a, and 3a preferentially interacting with D4, D2, and D3, respectively. To complete this set, the methylthio analogues 2b and 3b exceeding the affinity of 2a and 3a by one order of magnitude and the structural intermediate 1b were synthesized. These chemically similar but biologically divergent target compounds served as molecular probes for radioligand displacement experiments, mutagenesis, and docking studies on homology models based on the recent crystal structure of the beta2-adrenergic receptor. Specific interactions with the highly conserved amino acids Asp3.32 and His6.55 and less conserved residues at positions 2.61, 2.64, 3.28, and 3.29 were identified. Inclusion of a carefully modeled extracellular loop 2 displayed two nonconserved residues in EL2 that differently contribute to ligand binding. Obviously, subtype selectivity is caused by nonconserved but frequently mediated by conserved amino acids.

Droperidol has comparable clinical efficacy against both nausea and vomiting.

Br J Anaesth. 2009 Sep; 103(3): 359-63
Apfel CC, Cakmakkaya OS, Frings G, Kranke P, Malhotra A, Stader A, Turan A, Biedler A, Kolodzie K

BACKGROUND: Droperidol is commonly noted to be more effective at preventing postoperative nausea (PON) than vomiting (POV) and it is assumed to have a short duration of action. This may be relevant for clinical decisions, especially for designing multiple-drug antiemetic regimens. METHODS: We conducted a post hoc analysis of a large multicentre trial. Within this trial, 1734 patients underwent inhalation anaesthesia and were randomly stratified to receive several antiemetic interventions according to a factorial design, one of which was droperidol 1.25 mg vs placebo. We considered differences to be significant when: (i) point estimates of one outcome are not within the limits of the confidence interval (CI) of the other outcome; and (ii) differences in risk ratio (also known as relative risks, RR) are at least 20%. RESULTS: Over 24 h, nausea was reduced from 42.9% in the control to 32.0% in the droperidol group, corresponding to a relative risk (RR) of 0.75 (95% CI from 0.66 to 0.84). Vomiting was reduced from 15.6% to 11.8%, and therefore associated with a similar RR of 0.76 (0.59-0.96). In the early postoperative period (0-2 h), droperidol prevented nausea and vomiting similarly, with an RR of 0.57 (0.46-0.69) for nausea and 0.56 (0.37-0.85) for vomiting. In the late postoperative period (2-24 h), the RR was again similar with 0.83 (0.72-0.96) for nausea compared with 0.89 (0.66-1.18) for vomiting but significantly less compared with the early postoperative period. CONCLUSIONS: We conclude that droperidol prevents PON and POV equally well, yet its duration of action is short-lived.