Research and identification of tranquillizers - use of retention index. (1/98)
At the request of the Service des Haras, our laboratory works on the toxicological problems of the sport-horse. These studies have resulted in the setting up of an anti-doping control for equestrian competitions of various types, not only flat racing. During events, horses, must be calm and docile to the riders' order. Frequently, the latter use tranquillizers to try and win events. The analytical method for the research and identification of these compounds is described. The technique involves successively: 1. alkalinisation of the sample - saliva, blood or urine after enzymatic hydrolysis. 2. extraction with diethyl ether - the recovery is 70% to 90% depending upon the drug. 3. determination by gas-liquid chromatography with use of a retention index for qualitative analysis. We can detect up to fifteen tranquillizers in any one sample, even when present at such low concentrations as found in saliva. The use of the retention index is a reliable method for qualitative analysis. For example, the method has been used for three years, during which period the rentention index of acetylpromazine remained at 3240 +/- 7. The chromatographic analysis was performed on 3% OV-17 at 290 degrees. The chromatographic analysis has been performed by three columns of different polarity (OV-1; OV-17; SP-2250). If on the three columns, the retention index of one peak is the same as that of the tranquilizer, a further confirmation is made with the use of a thermionic detector specific for nitrogenous drugs. In conclusion, this method which is sufficiently precise and specific has been used for anti-doping control. (+info)Densitometric determination of impurities in pharmaceuticals. Part VI. Determination of 4,4-bis[4-(p-chlorophenyl)- 4-hydroxypiperidino]butyrophenone in haloperidol. (2/98)
A chromatographic and densitometic method for identification and quantitative determination of 4,4-bis[4-(p-chlorophenyl)-4-hydroxypiperidino]butyrophenone as an impurity in haloperidol pharmaceutical has been developed. The HPTLC plates and chloroform-methanol-ammonium hydroxide 25% (90:9:1) were used for chromatographic separation as stationary and mobile phases respectively. Detection has been carried out in UV at lambda = 350 nm. The determination could be made directly without preliminary component separation by extraction. Based on the statistical analysis of obtained results, it was found that the new method is accurate and repeatable. (+info)Anaesthetic agents inhibit gastrin-stimulated but not basal histamine release from rat stomach ECL cells. (3/98)
By mobilizing histamine in response to gastrin, the ECL cells in the oxyntic mucosa play a key role in the control of the parietal cells and hence of gastric acid secretion. General anaesthesia suppresses basal and gastrin- and histamine-stimulated acid secretion. The present study examines if the effect of anaesthesia on basal and gastrin-stimulated acid secretion is associated with suppressed ECL-cell histamine secretion. A microdialysis probe was implanted in the submucosa of the ventral aspect of the acid-producing part of the stomach (32 rats). Three days later, ECL-cell histamine mobilization was monitored 2 h before and 4 h after the start of intravenous infusion of gastrin (5 nmol kg(-1) h(-1)). The rats were either conscious or anaesthetized. Four commonly used anaesthetic agents were given 1 h before the start of the experiments by intraperitoneal injection: chloral hydrate (300 mg kg(-1)), pentobarbitone (40 mg kg(-1)), urethane (1.5 g kg(-1)) and a mixture of fluanisone/fentanyl/midazolam (15/0.5/7.5 mg kg(-1)). In a parallel series of experiments, basal- and gastrin-induced acid secretion was monitored in six conscious and 25 anaesthetized (see above) chronic gastric fistula rats. All anaesthetic agents lowered gastrin-stimulated acid secretion; also the basal acid output was reduced (fluanisone/fentanyl/midazolam was an exception). Anaesthesia reduced gastrin-stimulated but not basal histamine release by 55 - 80%. The reduction in gastrin-induced acid response (70 - 95%) was strongly correlated to the reduction in gastrin-induced histamine mobilization. The correlation is in line with the view that the reduced acid response to gastrin reflects impaired histamine mobilization. Rat stomach ECL cells were purified by counter-flow elutriation. Gastrin-evoked histamine mobilization from the isolated ECL cells was determined in the absence or presence of anaesthetic agents in the medium. With the exception of urethane, they inhibited gastrin-evoked histamine secretion dose-dependently, indicating a direct effect on the ECL cells. Anaesthetized rats are widely used to study acid secretion and ECL-cell histamine release. The present results illustrate the short-comings of such an approach in that a number of anaesthetic agents were found to impair not only acid secretion but also the secretion of ECL-cell histamine - some acting in a direct manner. (+info)Cardiovascular effects of endothelin-1 and endothelin antagonists in conscious, hypertensive ((mRen-2)27) rats. (4/98)
SB 209670 is a potent antagonist of the vasoconstrictor (ET(A)- and ET(B)-receptor-mediated) and vasodilator (ET(B)-receptor-mediated) effects of endothelin, whereas SB 234551 is relatively selective for the constrictor (ET(A)-receptor-mediated) effects. Since we had previously found SB 209670 exerted antihypertensive, vasodilator effects in conscious, heterozygous, transgenic ((mRen-2)27) (abbreviated to TG) rats, here we compared the two antagonists in that model, and assessed their chronic effects on responses to exogenous endothelin-1. We did this to test our global hypothesis, namely, that SB 209670, but not SB 234551, would cause inhibition of the depressor effects of exogenous endothelin-1 in vivo, and that this differential effect would be associated with a more marked antihypertensive action of SB 234551 in TG rats. SB 209670 and SB 234551 (infused for 50 h) exerted similar, sustained, antihypertensive effects in TG rats. The antihypertensive effects of the antagonists occurred at times when the pressor effects of exogenous endothelin-1 were not significantly inhibited. Furthermore, SB 234551 did not exert a greater antihypertensive effect than SB 209670 at a time (i.e., 2 - 4 h) when the depressor effects of endothelin-1 were abolished by the latter, but not by the former (although this differential action was lost after 24 h infusion). The results caused us to reject the hypothesis that selective antagonism of the vasoconstrictor effects of endothelin-1 would result in SB 234551 exerting a greater antihypertensive effect than SB 209670 in TG rats. (+info)A novel cytochrome P450 enzyme responsible for the metabolism of ebastine in monkey small intestine. (5/98)
Small intestinal microsomes of cynomolgus monkeys were found to catalyze hydroxylation and dealkylation of an H(1)-antihistamine prodrug, ebastine. To identify the main enzyme responsible for ebastine hydroxylation, which has been hitherto unknown, we purified two cytochrome P450 isoforms, named P450 MI-2 and P450 MI-3, from the intestinal microsomes on the basis of the hydroxylation activity. P450 MI-2 and P450 MI-3 showed the respective apparent molecular weights of 56,000 and 53,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The internal amino acid sequence of P450 MI-2 had high similarity with those of human CYP4F2, CYP4F3, and CYP4F8. The first 27 amino acid residues of P450 MI-3 were highly homologous with those of monkey CYP3A8 and human CYP3A4/5/7. Furthermore, P450 MI-2 and P450 MI-3 were recognized by anti-CYP4F and anti-CYP3A antibodies, respectively, in immunoblot analysis and catalyzed leukotriene B(4) omega-hydroxylation and testosterone 6beta-hydroxylation, which are known to be mediated by CYP4F and CYP3A, respectively. Although both enzymes had ebastine hydroxylation activity, the V(max) value of P450 MI-2 was much higher than that of P450 MI-3 (37.0 versus 0.406 nmol/min/nmol of P450), and the former K(M) (5.1 microM) was smaller than the latter K(M) (10 microM). Anti-CYP4F antibody inhibited the hydroxylation in small intestinal microsomes strongly (70%), but anti-CYP3A antibody did not. These results indicate that P450 MI-2 belongs to the CYP4F subfamily and is mainly responsible for hydroxylation of ebastine in monkey small intestinal microsomes. This suggests that the small intestinal CYP4F enzyme, P450 MI-2, can play an important role in the metabolism of drugs given orally. (+info)Gene replacement analysis of the butyrolactone autoregulator receptor (FarA) reveals that FarA acts as a Novel regulator in secondary metabolism of Streptomyces lavendulae FRI-5. (6/98)
IM-2 [(2R,3R,1'R)-2-1'-hydroxybutyl-3-hydroxymethyl gamma-butanolide] is a gamma-butyrolactone autoregulator which, in Streptomyces lavendulae FRI-5, switches off the production of D-cycloserine but switches on the production of a blue pigment and several nucleoside antibiotics. To clarify the in vivo function of an IM-2-specific receptor (FarA) in the IM-2 signaling cascade of S. lavendulae FRI-5, a farA deletion mutant was constructed by means of homologous recombination. On several solid media, no significant difference in morphology was observed between the wild-type strain and the farA mutant (strain K104), which demonstrated that the IM-2-FarA system does not participate in the morphological control of S. lavendulae FRI-5. In liquid media, the farA mutant overproduced nucleoside antibiotics and produced blue pigment earlier than did the wild-type strain, suggesting that the FarA protein acts primarily as a negative regulator on the biosynthesis of these compounds in the absence of IM-2. However, contrary to the IM-2-dependent suppression of D-cycloserine production in the wild-type strain, overproduction of D-cycloserine was observed in the farA mutant, indicating for the first time that the presence of both IM-2 and intact FarA are necessary for the suppression of D-cycloserine biosynthesis. (+info)Effects of supratherapeutic doses of ebastine and terfenadine on the QT interval. (7/98)
AIMS: The objective of this study was to compare the effects of high doses of ebastine with terfenadine and placebo on QTc. METHODS: Thirty-two subjects were randomly assigned to four treatments (ebastine 60 mg x day(-1), ebastine 100 mg x day(-1), terfenadine 360 mg x day(-1), placebo) administered for 7 days. Serial ECGs were performed at baseline and day 7 of each period. QT interval was analysed using both Bazett (QTcB) and Fridericia (QTcF) corrections. RESULTS: Ebastine 60 mg (+ 3.7 ms) did not cause a statistically significant change in QTcB compared with placebo (+ 1.4 ms). The mean QTcB for ebastine 100 mg was increased by + 10.3 ms which was significantly greater than placebo but was significantly less (P < 0.05) than with terfenadine 360 mg (+ 18.0 ms). There were no statistically significant differences in QTcF between ebastine 60 mg (-3.2 ms) or ebastine 100 mg (1.5 ms) and placebo (-2.1 ms); although terfenadine caused a 14.1 ms increase which was significantly different from the other three treatments. The increase in QTcB with ebastine most likely resulted from overcorrection of the small drug-induced increase in heart rate. CONCLUSIONS: Ebastine at doses up to five times the recommended therapeutic dose did not cause clinically relevant changes in QTc interval. (+info)Transport characteristics of ebastine and its metabolites across human intestinal epithelial Caco-2 cell monolayers. (8/98)
The transport characteristics of a selective peripheral H1 receptor antagonist, ebastine, a substrate for cytochrome P450 3A4, and its three major metabolites, i.e., the hydroxy metabolite of ebastine (M-OH), the pharmacologically active metabolite carebastine (Car), and the desbutyrophenone metabolite (des-BP), were studied in cultured human intestinal Caco-2 cells expressing a drug efflux pump, P-glycoprotein (P-gp), on the apical membrane. The polarized transport of [3H]cyclosporin A (CyA), mediated by P-gp in the basolateral to apical direction across the Caco-2 cell monolayers, was affected by the presence of ebastine in a concentration-dependent manner and significant inhibition was observed at high concentrations (>50 microM). M-OH (300 microM) also significantly inhibited whereas Car and des-BP did not. Although no marked polarized transport of [14C]ebastine in a secretory direction was observed in the Caco-2 systems, the flux in the basolateral to apical direction was slightly higher than that in the opposite direction at concentrations less than 30 microm. [14C]Ebastine (2 microM) uptake from the apical side was significantly increased in the presence of an excess of cold CyA, suggesting that the efflux process mediated by P-gp may be involved in the ebastine uptake by Caco-2 cells. Collectively, these results indicate that ebastine (and presumably M-OH) is transported via P-gp in Caco-2 cells, however, the affinity for P-gp is very low. It is unlikely that the secretory transport of ebastine mediated by P-gp will dramatically affect overall intestinal absorption in vivo because efficient passive diffusion of this drug should occur due to its high lipophilicity. However, it may be advantageous for its efficient first-pass metabolism. (+info)
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Haloperidol (Norodol)
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Butyrophenone
... is an organic compound with the formula C6H5C(O)C3H7. It is a colorless liquid. The butyrophenone structure-a ... Some of these butyrophenones are used to treat various psychiatric disorders such as schizophrenia, as well as acting as ... Examples of butyrophenone-derived pharmaceuticals include: Haloperidol, the most widely used classical antipsychotic drug in ... Grogan, Charles H.; Rice, Leonard M. (1967). "Ω-Azabicyclic Butyrophenones". Journal of Medicinal Chemistry. 10 (4): 621-623. ...
Fluanisone
... is a typical antipsychotic and sedative of the butyrophenone chemical class. It is used in the treatment of ... Enciprazine BMY-14802 Azaperone Janssen PA (1967). "Haloperidol and related butyrophenones". In Gordon M (ed.). ... Butyrophenone antipsychotics, Fluoroarenes, Phenol ethers, Piperazines, Phenylpiperazines, Typical antipsychotics, All stub ...
Parkinson's disease
... butyrophenones (haloperidol, benperidol, etc.); metoclopramide and Tetrabenazine. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine ...
Leonard Jan Le Vann
Le Vann, L. J. (1968). A new butyrophenone: Trifluperidol. A psychiatric evaluation in a pediatric setting Canadian Psychiatric ...
Trifluperidol
... is a typical antipsychotic of the butyrophenone chemical class. It has general properties similar to those of ... Gallant DM, Bishop MP, Timmons E, Steele CA (November 1963). "Trifluperidol: a butyrophenone derivative". The American Journal ... Butyrophenone antipsychotics, Janssen Pharmaceutica, Trifluoromethyl compounds, Typical antipsychotics, All stub articles, ...
Moperone
... (Luvatren, since discontinued) is a typical antipsychotic of the butyrophenone class which is marketed in Japan for ... Gross, H; Kaltenbäck, E (1969). "The clinical position of moperone among the butyrophenones". Nordisk Psykiatrisk Tidsskrift. ... Butyrophenone antipsychotics, Fluoroarenes, 4-Phenylpiperidines, Typical antipsychotics, 4-Tolyl compounds, All stub articles, ...
Valerophenone
Acetophenone Butyrophenone Propiophenone Milstein, D.; Stille, J. K. (1978). "A general, selective, and facile method for ...
Bromperidol
... , sold under the brand names Bromidol and Impromen among others, is a typical antipsychotic of the butyrophenone ... Dubinsky B, McGuire JL, Niemegeers CJ, Janssen PA, Weintraub HS, McKenzie BE (1982). "Bromperidol, a new butyrophenone ... Pöldinger W, Bures E, Haage H (1977). "Clinical study with bromperidol, a new butyrophenone derivative". International ... Butyrophenone antipsychotics, Aromatic ketones, Fluoroarenes, Janssen Pharmaceutica, Tertiary alcohols, Typical antipsychotics ...
Lenperone
... (Elanone-V) is a typical antipsychotic of the butyrophenone chemical class. It was first reported as an anti-emetic ... Marketed butyrophenones with approval status and indication in Miller AC, Khan AM, Castro Bigalli AA, Sewell KA, King AR, ... Butyrophenone antipsychotics, Fluoroarenes, Piperidines, Typical antipsychotics, Veterinary drugs, All stub articles, Nervous ... "Treatment of Acute Schizophrenia with a New Butyrophenone-Lenperone". Journal of Clinical Pharmacology. 15 (2-3): 187-90. doi: ...
Methamphetamine
... treatment with a benzodiazepine versus a butyrophenone". Eur. J. Emerg. Med. 4 (3): 130-135. doi:10.1097/00063110-199709000- ...
Aceperone
... is a neuroleptic drug of the butyrophenone class. It is an α-noradrenergic blocking drug developed by Janssen ... Butyrophenone antipsychotics, Fluoroarenes, 4-Phenylpiperidines, Typical antipsychotics, All stub articles, Nervous system drug ...
Postoperative nausea and vomiting
Butyrophenones are typically administered as a single injection at the end of surgery. Adverse effects include prolongation of ...
Carpipramine
It is structurally related to both tricyclics like imipramine and butyrophenones like haloperidol. Clocapramine Mosapramine ...
Substantia nigra
These antagonists include first generation (typical) antipsychotics such as butyrophenones, phenothiazines, and thioxanthenes. ...
Effects of hormones on sexual motivation
Benperidol or butyrophenone and the antiandrogen cyproterone acetate also used. Simpson ER, Jones ME (2006). "Of mice and men: ...
Neuroleptanalgesic
Iorio, M. A.; Paszkowska Reymer, T.; Frigeni, V. (1987). "Combined analgesic/neuroleptic activity in N-butyrophenone prodine- ...
Estradiol undecylate
Benperidol or butyrophenone and the antiandrogen cyproterone acetate also used. Kennedy BJ (April 1967). "Effect of massive ...
Estradiol (medication)
Benperidol or butyrophenone and the antiandrogen cyproterone acetate also used. Chatz, T.L. (June 1972). "Recognizing and ...
Typical antipsychotic
Another prominent grouping of antipsychotics are the butyrophenones, an example of which is haloperidol. The newer, second- ...
Actinometer
Organic actinometers like butyrophenone or piperylene are analysed by gas chromatography. Other actinometers are more specific ...
Dopamine hypothesis of schizophrenia
This observation was subsequently extended to other antipsychotic drug classes, such as butyrophenones including haloperidol. ...
Hyperprolactinaemia
These drugs include the typical antipsychotics: phenothiazines such as chlorpromazine (Thorazine), and butyrophenones such as ...
Domperidone
... is a benzimidazole derivative and is structurally related to butyrophenone neuroleptics like haloperidol. ... Domperidone, a benzimidazole derivative, is structurally related to the butyrophenone tranquilizers (eg, haloperidol (Haldol, ...
Pleurothotonus
K. Ekbom, H. Lindholm and L. Ljungerberg, New dystonic syndrome associated with butyrophenone therapy. Z Neurol, 202 (1972), pp ...
Lumateperone
... , sold under the brand name Caplyta, is an atypical antipsychotic medication of the butyrophenone class. It is ...
Spiperone
... is a typical antipsychotic and research chemical belonging to the butyrophenone chemical class. It is licensed for clinical use ... Butyrophenone antipsychotics, D2 antagonists, Fluoroarenes, Imidazolidinones, Spiro compounds, Typical antipsychotics). ...
Risperidone
Although not a butyrophenone, it was developed with the structures of benperidol and ketanserin as a basis. It has actions at ...
History of general anesthesia
Janssen synthesized nearly all of the butyrophenone class of antipsychotic agents, beginning with haloperidol (1958) and ...
Neuroleptic malignant syndrome
Individuals using butyrophenones (such as haloperidol and droperidol) or phenothiazines (such as promethazine and ...
Clocapramine
1983). "Comparison of efficacy of timiperone, a new butyrophenone derivative, and clocapramine in schizophrenia: a multiclinic ...
Butyrophenone influences on the opiate receptor<...
Creese, Ian ; Feinberg, Andrew P. ; Snyder, Solomon H. / Butyrophenone influences on the opiate receptor. In: European Journal ... Creese, I., Feinberg, A. P., & Snyder, S. H. (1976). Butyrophenone influences on the opiate receptor. European Journal of ... Butyrophenone influences on the opiate receptor. / Creese, Ian; Feinberg, Andrew P.; Snyder, Solomon H. ... Creese, I, Feinberg, AP & Snyder, SH 1976, Butyrophenone influences on the opiate receptor, European Journal of Pharmacology ...
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Words with ENO
Phenothiazines4
- Drug-induced parkinsonism results from dopamine receptor block by drugs such as phenothiazines, butyrophenones, and metoclopramide. (ispub.com)
- Available antiemetics, such as phenothiazines (chlorpromazine and prochlorperazine) and substituted benzamides (metoclopramide), were known to affect these receptors, as were butyrophenones (haloperidol and droperidol). (cancernetwork.com)
- Drugs that act primarily on the central nervous system receptors or the vestibular system include butyrophenones (e.g., haloperidol), phenothiazines (e.g., prochlorperazine, chlorpromazine), antihistamines (e.g., cyclizine) and anticholinergics (e.g., hyoscine). (aafp.org)
- Dopamine receptor blockers such as the phenothiazines, butyrophenones and substituted benzamides have been among the most effective agents. (elsevier.com)
Haloperidol3
- A butyrophenone with general properties similar to those of HALOPERIDOL. (nih.gov)
- Haloperidol is a butyrophenone derivative with tranquilizer/antipsychotic properties that are effective in the management of hyperactivity, agitation, and anxiety in humans. (vin.com)
- A spiro butyrophenone analog similar to HALOPERIDOL and other related compounds. (nih.gov)
Metoclopramide1
- Extrapyramidal effects of metoclopramide also may be increased with concurrent use of phenothiazine tranquilizers, narcotics, and butyrophenones. (wedgewoodpharmacy.com)
Antipsychotic1
- In most cases, they occur in older psychotic patients who are in institutions and in whom long-term treatment with antipsychotic drugs of the phenothiazine and butyrophenone groups is being carried out. (longecity.org)
Haloperidol2
- Sixteen chemical analogues of the butyrophenone haloperidol were tested on the dopamine-sensitive adenylate cyclase, and the results showed a good correlation between inhibitory potency in this system and the known effects of these compounds as apomorphine antagonists in vivo . (aspetjournals.org)
- Another prominent grouping of antipsychotics are the butyrophenones, an example of which would be haloperidol. (fichesmetier.com)
Chlorpromazine1
- None of these effects, however, occurred at very low drug concentrations, and the butyrophenones were no more potent than chlorpromazine. (aspetjournals.org)
Antipsychotic1
- Haldol antipsychotic remedy, butyrophenone derivative. (mymedic-rx.com)
Derivative2
- It is a derivative of butyrophenone and it acts by blocking the effects of dopamine, a chemical in the brain that affects thinking, behavior and feelings. (news-medical.net)
- Benperidol is a drug which is a highly potent butyrophenone derivative. (fandom.com)
Neuroleptic2
- Azaperone is a neuroleptic in the butyrophenone class of tranquilizers. (allenpress.com)
- Title does this new psychopharmacology was the rst butyrophenone neuroleptic. (willherndon.org)
Potent1
- As a result, fluoro butyrophenones are much more potent than amphetamines and have the potential to be abused. (pharmaguideline.com)
Drugs1
- The discovery of fluoro butyrophenones has created a new class of psychotropic drugs. (pharmaguideline.com)
Treatment2
- In the process I have learned a great deal about the habit of termites, the length of snake's tails, the meaning of the Kookaburra's raucous cry, the length of the vagus nerve in the sleeping lizard, the eccentricities of lightening, the dermatological metamorphoses of chameleons, the ecology of my own garden and, en passant, something of the causes and effective treatment of manic-depressive illness. (inhn.org)
- Leong L, Kelly A. Are butyrophenones effective for the treatment of primary headache in the emergency department? (aliem.com)