Disease relevance of PROMETHAZINE HYDROCHLORIDE

• In animals exposed to hypoxemia plus right carotid artery occlusion (oligemia) the promethazine treated group (25 mg/kg-1) showed significantly lower ATP and higher AMP contents which suggested an adverse effect on the metabolism of the acutely hypoxic-oligemic brain [1].
• Intramuscular ketorolac 60 mg, meperidine 50 mg plus promethazine 25 mg, and normal saline were compared in acute exacerbations of tension-type headache [2].
• Patients were excluded if they suffered from a neurodegenerative disorder or were exposed to anticholinergics, benzodiazepines, promethazine, carbamazepine, phenytoin, or levodopa during the study [3].
• These properties have made promethazine a candidate for use in environments such as microgravity, which provoke emesis and motion sickness [4].
• Traditional antiemetics, including anticholinergics (e.g., scopolamine), antihistamines (e.g., dimenhydrinate), phenothiazines (e.g., promethazine), butyrophenones (e.g., droperidol), and benzamide (e.g., metoclopramide), are used for the control of PONV [5].

Psychiatry related information on PROMETHAZINE HYDROCHLORIDE

• There was an overall significant increase (impairment) in recognition, motor and total reaction time (P < 0.05), and both the tracking accuracy and reaction time aspects of CTT were significantly impaired (P < 0.05) following the administration of promethazine [6].
• Promethazine has been reported to cause significant sedation, agitation, hallucinations, seizures, dystonic reactions, and possibly apparent life-threatening events or sudden infant death syndrome [7].
• The administration of diphenhydramine (20 mg kg(-1) s.c.), pyrilamine (15 mg kg(-1) s.c.) and promethazine (6 mg kg(-1) s.c.) produced an increase of the pain threshold which peaked 15 min after injection [8].
• The REM-depressing effect of promethazine together with its relatively weak REM-rebound effect may explain its value in the treatment of withdrawal symptoms following abuse of alcohol and barbiturates [9].
• An earlier study tested the effects of promethazine on cognitive and psychomotor performance and motion sickness tolerance in a rotating chair [10].

High impact information on PROMETHAZINE HYDROCHLORIDE

• Specifically, promethazine protected primary neuronal cultures subjected to oxygen-glucose deprivation and reduced infarct size and neurological impairment in mice subjected to middle cerebral artery occlusion/reperfusion [11].
• Histamine at a concentration of 10(-7) M was found to have a significant stimulatory effect on cell proliferation (p less than 0.001), and this effect was blocked by promethazine and clemastine but not by cimetidine [12].
• Propranolol, phentolamine, atropine, and promethazine did not affect the hypotensive action of bPTH-(1-34) in rats and dogs. bPTH-(1-34) decreased perfusion pressure in rat hindlimbs perfused in situ with Ringer's solution and was a vasodilator in dog kidneys perfused in vitro with Ringer's solution [13].
• Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation [14].
• When cells containing DNA lesions are treated with calmodulin inhibitors (W-7, phenothiazine, promethazine), the amount of lesions is increased, in all probability due to reduced DNA repair [15].

Chemical compound and disease context of PROMETHAZINE HYDROCHLORIDE

• We conclude that promethazine and diazepam depress arousal responses in sleeping lambs leading to profound hypoxia, and that this may be due to impaired sensitivity to augmented respiratory efforts and other physiologic changes during airflow obstruction [16].
• Male mixed-breed dogs were used to evaluate the effectiveness of cimetidine (Cim), promethazine (Pro), and thiethylperazine (Thi), singly and in combination, to raise the threshold for radiation-induced emesis [17].
• The effect of the administration of pertussis toxin as well as modulators of different subtypes of K+ channels on the antinociception induced by the H1-antihistamines pyrilamine, diphenhydramine and promethazine was evaluated in the mouse hot plate test [18].
• Bilateral vagotomy, BW 755c, glibenclamide, idazoxan, propranolol, methylatropine, methysergide or promethazine pretreatment failed to modify the hypotension induced by ET-1 (0.25 nmol/kg i.v.), but this effect was blocked entirely when ET-1 was injected 8 min after starting an i.v. infusion of ET-1 (0.1 nmol/kg/min for 10 min) [19].
• Intrafascicular injection caused diffuse axonal injury in the promethazine and dimenhydrinate groups, while prochlorperazine caused only focal injury [20].

Biological context of PROMETHAZINE HYDROCHLORIDE

• The effect of histamine on secretogranin II gene-expression was abolished by the H1 receptor antagonist promethazine but not by the H2 blocker cimetidine [21].
• Effects of promethazine on the energy metabolism of normoxic and hypoxic rat brain [1].
• The metabolic effects of intraperitoneal administration of promethazine on normoxic, hypoxemic and hypoxemic-oligemic rat brain were assessed by measurement of the cerebral contents of energy phosphates, and selected glycolytic-citric acid cycle intermediates [1].
• These data, when considered together with the hepatoprotective effects of promethazine, suggest that lipid peroxidation is of relatively more importance than covalent binding in the pathogenesis of CCl4-induced liver necrosis [22].
• A shorter side chain (e.g., promethazine) causes radical dimerization and pronounced hydroxylation, regardless of external nucleophiles [23].

Anatomical context of PROMETHAZINE HYDROCHLORIDE

• This hepatoprotective property has been investigated with regard to the free radical scavenging and antioxidant properties of promethazine using isolated hepatocytes and microsomal suspensions [22].
• The inhibition of CYP2D6-catalysed bufuralol 1'-hydroxylase by various histamine H3 antagonists including promethazine suggested that promethazine and some other histamine H1 antagonists could be inhibitors of this P450 in human liver microsomes [24].
• Blockade of Na+ current by promethazine in guinea-pig ventricular myocytes [25].
• Effects of promethazine hydrochloride on the metabolism of rabbit alveolar macrophages [26].
• The H1-receptor antagonists (+)-chlorpheniramine and promethazine similarly had no effect on the EC50 value for histamine in guinea-pig ileum, while promethazine competitively antagonized the muscarinic receptor-mediated inositol phospholipid response in this tissue (Ka 3.6 X 10(7)M-1) [27].

Associations of PROMETHAZINE HYDROCHLORIDE with other chemical compounds

• A comparative study of the interaction of chlorpromazine, trifluoperazine, and promethazine with mouse brain tubulin [28].
• The promethazine hydroxylase in human liver microsomes was inhibited by SKF-525A, propranolol, sparteine, quinidine and anti-CYP2D6 serum suggesting involvement of a P450 related to CYP2D6 [24].
• Compound 2 [RS-49014, 3,4-dihydro-1,3-dimethyl-7-[3-[4-[3-(phenylthio)propyl]piperazin-1 -yl]- 2-hydroxypropyl]-1H-purine-2,6-dione] was selected for clinical trials on the basis of a comparative pharmacological study with chlorpheniramine, ketotifen, promethazine, and theophylline [29].
• Protection against the PrP[118-135] peptide-induced OLG apoptosis by several antioxidant molecules, such as probucol, propylgallate, and promethazine, suggests that oxidative injuries contribute to the PrP[118-135] cytotoxicity to OLGs [30].
• Women in the intravenous analgesia group received 50 mg meperidine with 25 mg promethazine hydrochloride as an initial bolus, followed by 15 mg meperidine every 10 min as needed, using a patient-controlled pump [31].

Gene context of PROMETHAZINE HYDROCHLORIDE

• Microsomes from genetically-engineered human B-lymphoblastoid cells expressing CYP2D6 hydroxylated promethazine most efficiently as compared to other P450 forms, indicating that it was the principal P450 responsible for the metabolism of promethazine in human liver microsomes [24].
• Tricyclic antidepressants such as desipramine, imipramine and nortriptyline as well as phenothiazines such as fluphenazine, promethazine, chlorpromazine and trifluoperazine blocked the hSK3 channel with micromolar potencies [32].
• The hyperglycemic response to neurotensin was partially blocked by the histamine H-1 receptor blockers, diphenhydramine and promethazine, and by the H-2 receptor blocker, cimetidine [33].
• The enhancement of the depolarizing afterpotential by histamine was mimicked by the histamine H1-receptor agonist 2-thiazolylethylamine and was reduced or blocked by the H1-receptor antagonist promethazine, but was not blocked or reduced in the presence of the histamine H2-receptor antagonist, cimetidine [34].
• No effect on oedema formation was found when CGRP 300 pmol was co-administered with either promethazine or s(-)-propranolol (H1 and 5-HT1 receptor antagonists, respectively) [35].

Analytical, diagnostic and therapeutic context of PROMETHAZINE HYDROCHLORIDE

• METHODS: In 162 patients, conscious sedation during ICD placement was achieved with combined intravenous midazolam, morphine and promethazine (Phenergan) [36].
• Determination of promethazine in serum by liquid chromatography [37].
• Promethazine-HCl (Phenergan) in the treatment of rat cardiac allografts [38].
• On-column reduction of promethazine metabolite during gas chromatography [39].
• Because of promethazine's antihistaminic and anticholinergic properties, we expected that a 50-mg intramuscular injection of promethazine would affect sympathetically and vagally mediated cardiovascular mechanisms [4].

References