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PubMed2003

The relation of motion sickness to the spatial-temporal properties of velocity storage.

Tilting the head in roll to or from the upright while rotating at a constant velocity (roll while rotating, RWR) alters the position of the semicircular canals relative to the axis of rotation. This produces vertical and horizontal nystagmus, disorientation, vertigo, and nausea. With recurrent exposure, subjects habituate and can make more head movements before experiencing overpowering motion sickness. We questioned whether promethazine lessened the vertigo or delayed the habituation, whether habituation of the vertigo was related to the central vestibular time constant, i.e., to the time constant of velocity storage, and whether the severity of the motion sickness was related to deviation of the axis of eye velocity from gravity. Sixteen subjects received promethazine and placebo in a double-blind, crossover study in two consecutive 4-day test series 1 month apart, termed series I and II. Horizontal and vertical eye movements were recorded with video-oculography while subjects performed roll head movements of approx. 45 degrees over 2 s to and from the upright position while being rotated at 138 degrees /s around a vertical axis. Motion sickness was scaled from 1 (no sickness) to an endpoint of 20, at which time the subject was too sick to continue or was about to vomit. Habituation was determined by the number of head movements that subjects made before reaching the maximum motion sickness score of 20. Head movements increased steadily in each session with repeated testing, and there was no difference between the number of head movements made by the promethazine and placebo groups. Horizontal and vertical angular vestibulo-ocular reflex (aVOR) time constants declined in each test, with the declines being closely correlated to the increase in the number of head movements. The strength of vertiginous sensation was associated with the amount of deviation of the axis of eye velocity from gravity; the larger the deviation of the eye velocity axis from gravity, the more severe the motion sickness. Thus, promethazine neither reduced the nausea associated with RWR, nor retarded or hastened habituation. The inverse relationship between the aVOR time constants and number of head movements to motion sickness, and the association of the severity of motion sickness with the extent, strength, and time of deviation of eye velocity from gravity supports the postulate that the spatiotemporal properties of velocity storage, which are processed between the nodulus and uvula of the vestibulocerebellum and the vestibular nuclei, are likely to represent the source of the conflict responsible for producing motion sickness.

Adult↗
PubMed1978

The effects of an antihistamine and/or a glucocorticoid on the prolactin response to surgical procedures.

Prolactin (PRL) release in response to surgical stress has been demonstrated in a variety of species. Previous studies in rats indicate this response is blunted or blocked by pretreatment with either glucocorticoids or antihistamines. The present study was designed to investigate this phenomenon in man. Serum PRL levels before, during, and after major gynecologic surgery were measured in 20 women randomly assigned to one of four pretreatment regimens: (1) dexamethasone, (2) promethazine, (3) both agents, and (4) neither agent. Type of operation, preanesthetic medication, anesthetic agents, and estrogen status of patients were similar in all groups. Untreated controls exhibited the expected five- to tenfold increase in serum PRL concentration with surgery. Pretreatment with either dexamethasone or promethazine alone failed to suppress this response (in contrast to reported findings in the rat) and in fact promethazine appeared to cause an augmented response. However, patients given dexamethasone and promethazine together exhibited only a two- to threefold PRL increase, a significantly lesser response than that in any of the other groups. Thus, PRL release in response to general anesthesia and surgery is inhibited by the combination of an antihistamine (H-l) receptor antagonist and a glucocorticoid, whereas either agent alone has no suppressive effect.

Adult↗
PubMed1979

Evaluation of sedative/analgesic combination for postoperative pain.

Current pain concepts suggest a dual role in pain perception. Both motivational, effective, and somatosensory components are noted. Pain affects the patient's psyche and, conversely, the patient's state of mind modifies pain perception. Consequently, it might be expected that a sedative/analgesic combination might be more effective than either the sedative or the analgesic alone in controlling pain. A clinical study was carried out to compare a promethazine-A.P.C. combination with promethazine and A.P.C. alone. One hundred forty-nine patients undergoing third molar removal were studied, with each patient serving as his own control. The results indicated a significant difference between the promethazine-A.P.C. combination and prometazine alone or Phenergan alone. No significant difference was noted between the promethazine-A.P.C. combination and A.P.C. alone.

Anxiety↗
PubMed2005

The effectiveness of rescue antiemetics after failure of prophylaxis with ondansetron or droperidol: a preliminary report.

STUDY OBJECTIVES: To compare the effectiveness of treating established postoperative nausea and vomiting (PONV) with an antiemetic acting at a different receptor with that of treating PONV with the antiemetic used for prophylaxis. DESIGN: Analysis of data collected in a previously published randomized, double-blind, placebo-controlled study. SETTING: Outpatient surgical procedures from 50 institutions in North America. PATIENTS: Patients (N = 2061) undergoing outpatient surgical procedures planned to last no more than 2 hours. INTERVENTIONS: Patients were randomized to receive ondansetron 4 mg, droperidol 1.25, droperidol 0.625 mg, or placebo. In the postoperative anesthesia care unit, patients who developed PONV received rescue antiemetics at the discretion of the attending anesthesiologist. The following antiemetics were used for rescue: ondansetron 4 mg, droperidol 0.625 to 1.25 mg, metoclopramide 10 mg, promethazine 6.25 to 25 mg, and dimenhydrinate 25 to 50 mg. MEASUREMENTS: The complete response rate (no nausea, no emesis, and no need for further rescue) after administration of the rescue antiemetic in patients with established PONV was calculated. The complete response rate after administration of each of the different rescue antiemetics was compared with that after administration of the same antiemetic used for PONV prophylaxis. MAIN RESULTS: In patients who failed prophylaxis with ondansetron 4 mg, the complete response rate was significantly higher (P = .02) after rescue with promethazine 6.25 to 25 mg (78%) than after rescue with ondansetron 4 mg (46%). In patients who failed prophylaxis with droperidol 0.625 and 1.25 mg, the complete response rate was significantly higher after rescue with promethazine 6.25 to 25 mg (77%; P = .02) and dimenhydrinate 25 to 50 mg (78%; P = .04) than after rescue with droperidol 0.625 to 1.25 mg (56%). CONCLUSION: In patients who failed prophylaxis with ondansetron or droperidol, promethazine was significantly more effective than the agent used for prophylaxis for the treatment of PONV. In patients who failed prophylaxis with droperidol, dimenhydrinate was also more effective than droperidol for the treatment of established PONV in the postoperative anesthesia care unit.

Adult↗
PubMed1996

A pilot study of intravenous ondansetron for hyperemesis gravidarum.

OBJECTIVE: We attempted to determine whether the antiemetic ondansetron would be more effective than promethazine in treating hyperemesis gravidarum. STUDY DESIGN: Patients with hyperemesis gravidarum who required hospital admission were randomized to receive either intravenous ondansetron (n = 15) or intravenous promethazine (n = 15) in a double-blind manner. Severity of disease was determined by electrolyte status, weight loss, ketonuria, and prior use of outpatient antiemetics. Outcome variables included degree of nausea, weight gain during treatment, days of hospitalization, and number of medication doses. RESULTS: In this preliminary investigation ondansetron offered no advantage when compared with promethazine in the relief of nausea, weight gain, days of hospitalization (4.5 +/- 2.3 vs 4.5 +/- 1.5), and total doses of medication per hospitalization (2.1 +/- 1.2 vs 1.9 +/- 1.3). CONCLUSION: This preliminary trial of ondansetron demonstrated no benefit over promethazine in patients hospitalized for hyperemesis gravidarum.

Adult↗
PubMed1978

Comparative study of two long-acting tranquillizers for oral premedication.

Lorazepam 2.5 mg was compared with promethazine 50 mg as oral premedication in a double-blind study in women. The premedication was given at the same time to all patients on each operating list, and both drugs continued to be effective 6 h after ingestion. A similar number of patients considered each drug to have relieved anxiety and the amnesic effect of lorazepam was confirmed. However, the use of lorazepam alone was accompanied by significantly more salivation during and after anaesthesia than the use of promethazine, especially in patients in whom the trachea was intubated. There was also a higher frequency of vomiting during and after operation with lorazepam (seven of 67 patients) than after promethazine (one of 71 patients). Promethazine produced dyskinetic side-effects in six of 71 patients.

Administration, Oral↗
PubMed2000

Small-dose droperidol effectively reduces nausea in a general surgical adult patient population.

UNLABELLED: In this prospective, randomized, placebo-controlled study, we (1) determined whether 0.625 mg of IV droperidol given 30 min before emergence from general anesthesia reduces the incidence of immediate and delayed postoperative nausea and vomiting (PONV) in a general surgical adult patient population, and (2) compared the efficacy of droperidol, ondansetron, and promethazine for the rescue treatment of PONV. One hundred fifty adult patients receiving general anesthesia for >2 h received either droperidol (0.625 mg IV) or a placebo before emergence. Patients requiring treatment for PONV in the postanesthesia care unit were randomized to receive either droperidol (0.625 mg IV), ondansetron (4 mg IV), or promethazine (12. 5 mg IV). Droperidol effectively prevented PONV (6.8% in droperidol-treated patients versus 40.8% in placebo-treated patients, P: < 0.001). Droperidol, ondansetron, and promethazine were equally effective in treating established PONV, without significant differences in side effects or time to postanesthesia care unit discharge. IMPLICATIONS: Droperidol 0.625 mg IV before emergence from general anesthesia effectively reduces postoperative nausea and vomiting (PONV) in the general surgical population. Our randomized, double-blinded, placebo-controlled study demonstrated a reduction in PONV from 41% to 7%. Droperidol is a safe and inexpensive alternative to ondansetron. Droperidol, ondansetron, and promethazine are also equally effective in treating PONV in the postanesthesia care unit.

Anesthesia, General↗
PubMed2004

Stimulation of the semicircular canals via the rotary chair as a means to test pharmacologic countermeasures for space motion sickness.

OBJECTIVE: Space motion sickness is currently treated pharmacologically with the empiric use of the H1 antihistamine promethazine, but use of this intervention is limited by the side effect of significant sedation. This creates a dilemma, as full cognition is particularly important during the same conditions likely to exacerbate the symptoms of space motion sickness. Using overstimulation of the semicircular canals with a rotary chair as a paradigm for space motion sickness, we evaluated four medications, commonly used for the treatment of terrestrial motion sickness and vertigo, for their efficacy in alleviating the simulated symptoms of space motion sickness. STUDY DESIGN: Randomized, prospective, double-blind study. SETTING: Tertiary referral center. PATIENTS: Healthy male and female volunteers, 18 years of age or older, without history of neurologic or psychiatric disorders, and with no known allergies or any previous adverse reactions to the drugs used. INTERVENTIONS: Lorazepam 1 mg, meclizine 25 mg, promethazine 25 mg, scopolamine 0.4 mg, or placebo. MAIN OUTCOME MEASURE: The ability of each treatment to control the nausea and vomiting associated with our paradigm for space motion sickness was evaluated by measuring time of rotation pre- and posttreatment and time of symptom onset pre-and posttreatment. RESULTS: Only scopolamine effected a mean change in duration of rotation that reached statistical significance when compared with placebo (p <0.008), with a greater than 40% increase in rotation time. Results with promethazine were not statistically significant. CONCLUSION: Results showed a rank order of efficacy of scopolamine > promethazine > placebo > meclizine > lorazepam. Scopolamine significantly increased rotation time, but none of the treatments resulted in a significant delay to onset of symptoms.

Adolescent↗
PubMed1985

Chlorpromazine--a specific effect on breathlessness?

Previous work has left unresolved questions on whether promethazine reduces the sensation of breathlessness. This study was designed to provide a definitive answer and to determine the contributions from promethazine's major pharmacological actions. Twelve healthy subjects participated in a double-blind, within-subject comparison of promethazine and placebo each given acutely by mouth. Breathlessness was assessed with visual analogue scales during a progressive exercise test and was related to minute ventilation. Promethazine had no significant effect on breathlessness nor on the relationship between breathlessness and ventilation. The role of histamine-antagonism was investigated in a subgroup of the subjects by administration of mebhydrolin. No effect on breathlessness was detected. In contrast, the standard phenothiazine, chlorpromazine, caused a marked and statistically significant reduction in breathlessness without affecting ventilation and without causing detectable sedation. This unexpected finding merits further study in patients and is discussed with reference to the role of chlorpromazine as a constituent of Brompton's Mixture.

Adult↗
PubMed1995

Antihistamine activity, central nervous system and cardiovascular profiles of histamine H1 antagonists: comparative studies with loratadine, terfenadine and sedating antihistamines in guinea-pigs.

BACKGROUND: Sedation limits the clinical utility of classical H1 antihistamines, while newer antihistamines such as loratadine and terfenadine are non-sedating. However, clinical use of the terfenadine has been associated with rare but severe cardiac arrhythmias, in particular torsades de pointes. OBJECTIVE: To establish a quantitative experimental model for assessing the sedating and cardiotoxicity potential of non-sedating and sedating antihistamines. METHODS: Drugs were administered intravenously and the integrated amplitude of the cortical electroencephalogram (EEG) signal was recorded. The threshold dose that depressed EEG activity was compared with the dose required to inhibit by 50% the peripheral bronchospasm elicited by 10 micrograms/kg i.v., of histamine. In separate studies, the electrocardiogram (ECG) and cardiovascular effects of loratadine (30 and 100 mg/kg, i.v.), terfenadine (10 mg/kg, i.v.), promethazine (5 mg/kg, i.v.) and diphenhydramine (20 mg/kg, i.v.) were evaluated. RESULTS: The sedating antihistamines, diphenhydramine and promethazine, depressed the integrated EEG at doses between 0.6 and 2.0 times their peripheral antihistamine doses. Loratadine had no EEG depressant activity at 100 mg/kg, i.v., a dose more than 170 times its ED50 (0.58 mg/kg, i.v.) against histamine bronchospasm. We were unable to evaluate the EEG effects of terfenadine, because it produced cardiovascular collapse at 10 mg/kg, i.v. Loratadine and promethazine did not produce adverse cardiovascular effects, nor did they alter normal ECG activity. Diphenhydramine produced bradycardia followed by a transient hypertensive phase without affecting the QTc interval. In contrast, terfenadine elicited hypotension, bradycardia and significant arrhythmogenic activity, causing a prolongation of the QTc interval and a torsades de pointes--like ventricular arrhythmia. Pharmacokinetic studies after i.v. administration of loratadine (30 and 100 mg/kg) demonstrated plasma levels of loratadine and its major metabolite descarboethoxyloratadine to be several orders of magnitude greater than levels found in humans at the clinical dose of 10 mg. CONCLUSION: The CNS depressant effects of H1 antihistamines are promethazine approximately diphenhydramine >> loratadine = placebo. Of the non-sedating antihistamines, loratadine was devoid of adverse cardiovascular effects whereas terfenadine caused a pronounced disruption of the normal ECG, characterized by a torsades de pointes-like effect.

Animals↗
PubMed1996

Influence of sedation on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs.

Our aim was to determine the effects of two commonly used sedatives, promethazine and diazepam, on arousal and cardiorespiratory responses to airflow obstruction in sleeping lambs. In eight lambs fitted with obstructable rubber face masks, we recorded electrocortical, electroocular, and electromyographic activities to identify sleep-wake states; intrapleural pressure, heart rate, and percentage O2 saturation (Sao2) were also recorded. In each lamb, arousal and respiratory responses were measured after tidal airflow was obstructed during rapid eye movement (REM) and nonREM sleep. Each lamb was studied, on different days, when unsedated and after being mildly sedated with either promethazine or diazepam. Seven of the lambs were studied while sleeping after being sedated with promethazine (1.6 +/- 0.07 mg/kg, orally with milk) and six were studied after sedation with diazepam (0.31 +/- 0.03 mg/kg, intramuscularly). In unsedated lambs, airflow obstruction led to augmentation of respiratory efforts, bradycardia, hypoxemia, and arousal; in REM sleep, arousal was delayed and occurred at lower Sao2 (16 +/- 3 s; 75.3 +/- 3%) compared with nonREM sleep (8 +/- 1 s; 90 +/- 1%). Sedation increased the arousal latency in both REM and nonREM sleep and caused arousal to occur at lower Sao2; in some sedated lambs Sao2 fell to less than 30% before arousal. The augmentation of inspiratory and expiratory efforts immediately before arousal was increased after sedation. 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.

Animals↗
PubMed2005

Selective inhibition of brain Na,K-ATPase by drugs.

The effect of drugs from the class of cardiac (methyldigoxin, verapamil, propranolol), antiepileptic (carbamazepine), sedative (diazepam) and antihistaminic (promethazine) drugs on Na,K-ATPase activity of plasma membranes was studied in rat brain synaptosomes. Methyldigoxin in a concentration of 0.1 mmol/l inhibits enzyme activity by 80 %. Verapamil, propranolol and promethazine in concentrations of 20, 20 and 2 mmol/l respectively, entirely inhibit the ATPase activity. Carbamazepine and diazepam in concentrations of 0.02-60 mmol/l have no effect on the activity of this enzyme. According to the drug concentrations that inhibit 50 % of enzyme activity (IC(50)), the potency can be listed in the following order: methyldigoxin promethazine verapamil ? propranolol. From the inhibition of commercially available purified Na,K-ATPase isolated from porcine cerebral cortex in the presence of chosen drugs, as well as from kinetic studies on synaptosomal plasma membranes, it may be concluded that the drugs inhibit enzyme activity, partly by acting directly on the enzyme proteins. Propranolol, verapamil and promethazine inhibitions acted in an uncompetitive manner. The results suggest that these three drugs may contribute to neurological dysfunctions and indicate the necessity to take into consideration the side effects of the investigated drugs during the treatment of various pathological conditions.

Adenosine Triphosphate↗
PubMedDate not supplied

[A comparison of the child's behavior between two groups of oral sedative drugs].

The purpose of this study was to compare the child's behavior between the two groups of oral sedative drugs: a) Chloral hydrate and Promethazine and b) Hydroxyzine and Diazepam. Fourteen healthy children, aged 3 to 5 years old, participated in this study. All children exhibited negative behavior and required at least two restorative appointments with the use of oral sedative drugs and nitrous oxide-oxygen inhalation sedation. The drugs were randomly administered in a double-blind manner. The degree of sleep, crying, movement and overall behavior were evaluated during the operative procedures. With respect to sleeping, there was no significant difference in the child's behavior between the two drug groups. With respect to crying, the children who had Hydroxyzine and Diazepam cried significantly less than when they had Chloral hydrate and Promethazine at the time of injection and rubber dam placement (P less than 0.05). With respect to movement, the children who had Hydroxyzine and Diazepam moved significantly less than when they had Chloral hydrate and Promethazine at the time of injection, rubber dam placement, and the 60 minute interval (P less than 0.05). For overall behavior, the children who had Hydroxyzine and Diazepam behaved better than when they had Chloral hydrate and Promethazine (P less than 0.05).

Child Behavior↗
PubMed1985

Effects of some motion sickness suppressants on static and dynamic tracking performance.

Two studies examined the influence of three established antimotion sickness drugs on tracking performance in static (stationary) and dynamic (angular acceleration) conditions and on visual fixation ability during motion. In Study I, 40 young men were randomly assigned in equal numbers to either a control (lactose placebo), dimenhydrinate (50 mg), promethazine hydrochloride (25 mg), or mixture (25 mg promethazine plus 10 mg d-amphetamine) group. Study II used 30 new subjects equally divided into control, dimenhydrinate (100 mg), and promethazine (50 mg) groups. Following practice, tests were conducted prior to, and 1, 2, and 4 h after drug ingestion. The depressant drugs had little effect on static tracking, but impaired dynamic tracking performance and reduced ability to maintain visual fixation on a localizer/glide slope instrument due to increased ocular nystagmus. The mixture of promethazine plus d-amphetamine produced none of these deleterious effects.

Aerospace Medicine↗
PubMed1978

Chronic rhinitis in the pre-school child.

The etiologic role of atopy in chronic rhinitis in 40 infants and pre-school children was investigated and the long-term effectiveness and safety of promethazine studied during six to 48 months. Twenty children were clearly atopic and 16 were not. Four had incomplete laboratory evidence of atopy. In addition to clinical histories and physical findings, the subjects were evaluated by skin tests for common allergens. RAST tests, total IgE levels and absolute eosinophil counts. Promethazine in doses of 3 to 12 mg/kg/day (mean 8 mg) was administered in divided doses, four times a day for perennial rhinitis and on "as required" basis for recurrent and seasonal rhinitis. Side effects included drowsiness and irritability, which led to discontinuance of promethazine in one subject. There was no laboratory evidence of hematologic, renal or hepatic abnormalities. Promethazine was found to be an effective agent for symptom-control of chronic rhinitis in the pre-school child.

Asthma↗
PubMed2005

Enantioseparation of phenothiazines in cyclodextrin-modified capillary zone electrophoresis using sulfated cyclodextrins as chiral selectors.

In this study, enantioseparations of five phenothiazines, including promethazine, ethopropazine, trimeprazine, methotrimeprazine, and thioridazine, in CD-modified CZE using dual CD systems consisting of randomly sulfate-substituted CD (MI-S-beta-CD) and a neutral CD as chiral selectors in a citrate buffer (100 mM) at pH 3.0 were investigated. The results indicate that MI-S-beta-CD is an excellent chiral selector for enantioseparation of ethopropazine. The enantiomers of promethazine can also be baseline-resolved with MI-S-beta-CD at concentrations in the range of 0.5-1.0% w/v. On the other hand, thioridazine and trimeprazine interact strongly with neutral CDs. As a result, the enantioselectivity of these two phenothiazines is remarkably and synergistically enhanced with increasing the concentration of neutral CDs in the presence of MI-S-beta-CD and simultaneous enantioseparations of these phenothiazines, except for methotrimeprazine, could favorably be achieved with the use of dual CD systems. Moreover, by varying the concentration of beta-CD or gamma-CD at a fixed concentration of MI-S-beta-CD (0.75% w/v) reversal of the enantiomer migration order of promethazine occurred. This may be attributable to the opposite effects of charged and neutral CDs on the mobility of the enantiomers of promethazine.

Cyclodextrins↗
PubMed1984

Mechanisms of the killing of cultured hepatocytes by hydrogen peroxide.

Mechanisms of H2O2-induced cell injury were explored in primary cultures of rat hepatocytes. Cells prepared from male rats and cultured for 1 day prior to treatment were killed by H2O2 either added directly to the medium at 0.25-2 mM or generated in situ by glucose oxidase (0.25-2 U/ml) or xanthine oxidase (20-120 mM/ml) and 2 mM xanthine. Catalase protected the cells in each case. Lipid peroxidation as measured by the accumulation of malondialdehyde (MDA) preceded the cell death due to H2O2 added directly to the cultures or generated in the medium. The antioxidants N,N'-diphenyl-p-phenylenediamine (DPPD) and promethazine prevented the accumulation of MDA in both cases and protected the cells treated with H2O2 directly. DPPD and promethazine did not react directly with H2O2. Other antioxidants including butylated hydroxytoluene, vitamin E, and N-propylgallate had varied protective activity against the addition of H2O2 in proportion to their ability to reduce MDA accumulation. In glucose oxidase-treated cultures, DPPD and promethazine prevented the cell killing during the first hour but failed to protect between 1 and 3 h despite prevention of lipid peroxidation. The cell killing between 1 and 3 h in the presence of DPPD was prevented by catalase indicating its dependence upon continued generation of H2O2. Further addition of H2O2 in the presence of DPPD also increased the number of dead cells without lipid peroxidation. The data are consistent with at least two mechanisms of hepatocyte killing by H2O2. The first pathway is prevented by the antioxidants DPPD and promethazine and is very likely related to the peroxidation of membrane phospholipids. The second is independent of lipid peroxidation yet dependent upon the continued presence of H2O2.

Animals↗
PubMed1980

Histamine H1-receptors in the brain of the guinea-pig and the rat: differences in ligand binding properties and regional distribution.

1 The equilibrium dissociation constant, K(d), for mepyramine binding to a particulate fraction from rat brain, 9.1 nM, determined from inhibition of the binding of 1 nM [(3)H]-mepyramine, was distinctly higher than that, 0.83 nM, measured on an equivalent preparation from guinea-pig brain.2 In rat brain the dissociation constant for mepyramine, determined from the binding of [(3)H]-mepyramine sensitive to inhibition by 2 x 10(-6) M promethazine, was higher than the constant obtained from the inhibition of the binding of 1 nM [(3)H]-mepyramine by non-radioactive mepyramine. This suggests that the promethazine-sensitive binding of [(3)H]-mepyramine includes a lower affinity non-receptor component, which becomes apparent at higher concentrations of [(3)H]-mepyramine.3 In the guinea-pig the dissociation constant for mepyramine determined from inhibition of [(3)H]-mepyramine binding was in good agreement with the value obtained from inhibition of the contractile response of intestinal smooth muscle to histamine. No similar comparison was possible in the rat. Rat ileum was much less sensitive to histamine and the contraction produced was not inhibited by 10(-6) M mepyramine, indicating that it is not mediated by H(1)-receptors.4 Low levels of promethazine-sensitive [(3)H]-mepyramine binding were present in membrane fractions prepared from the longitudinal muscle from rat small intestine, but the characteristics of this binding suggest that it may be largely to lower affinity, non-receptor sites.5 Promethazine was practically equipotent as an inhibitor of [(3)H]-mepyramine binding in rat and guinea-pig brain. Chlorpheniramine showed stereospecificity in the rat as in the guinea-pig, although the potency of the (+)-isomer in the rat was only a tenth of that in the guinea-pig. Histamine had nearly the same IC(50) in both species.6 The evidence suggests that the high-affinity [(3)H]-mepyramine binding sites in rat brain can be described as H(1)-receptors, but that these differ structurally from H(1)-receptors in the guinea-pig.7 The regional distribution of [(3)H]-mepyramine binding in rat brain was not the same as that in guinea-pig brain, the most notable difference being the very much lower level in rat cerebellum compared to guinea-pig cerebellum.

Animals↗