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PubMed1988

Salivary response to olfactory food stimuli in anorexics and bulimics.

Salivary response to olfactory food stimuli was assessed in controls and in anorexia nervosa and bulimia in-patients before and after two months of treatment. Before treatment, anorexics salivated less then controls while bulimics salivated more than controls. Following treatment, the salivary responses of eating-disordered subjects were much closer to controls. Salivary response to food was correlated with a measure of variability in caloric consumption. There may be two styles of dietary restraint: strict, unrelenting dieting, or the "dieting drone", exemplified by anorexic patients, and variable, "fence-sitting" dietary restraint, exemplified by bulimic patients. It is suggested that this two-style theory is able to account for past contradictory findings of heightened or suppressed saliva flow rates in dieters.

Adolescent↗
PubMed1999

Tri-isobutylphosphate: a prenatal toxicity study in rats.

To assess the prenatal toxicity to rats of the anti-foaming agent, tri-isobutylphosphate (CAS 126-71-6), a study was conducted in which daily dosages of 0, 100, 300 and 1000 mg/kg were administered to different treatment groups by gavage from day 6 to 15 of pregnancy. Dams were killed and foetuses examined on day 20 of pregnancy. Maternal effects during the dosing period included a dosage-related increase in the frequency, persistence and severity of post dosing salivation in all test groups and significantly increased water consumption at 1000 mg/kg. Bodyweight gain at 1000 and 300 mg/kg was lower than that of controls but the differences were not statistically significant. The lowest dosage of 100 mg/kg could be considered as the maternal 'lowest observed adverse effect level' (LOAEL) or 'no observed adverse effect level' (NOAEL) according to whether increased salivation is perceived to be a true toxic effect or simply a reaction to the taste of the test material. Neither litter values nor the prevalence of foetuses with abnormalities indicated any embryotoxic effects (including teratogenicity) at any dosage. The most notable feature of the results was the occurrence of a cluster of foetuses with the congenital abnormality referred to as 'hunched posture syndrome' or 'squat foetus syndrome'. However, the incidence of this finding was similar to that noted among background data for the same strain and, in the absence of any other embryotoxic findings, was considered likely to have arisen coincidentally.

Animals↗
PubMed1990

Gustatory impairment and salivary gland pathophysiology in relation to oral cancer treatment.

Gustation and salivation were evaluated in 41 patients with oral carcinoma who were treated preoperatively with Peplomycin (PLM) or PLM + 5-FU + 60CO- radiation. Thresholds for sweet, salt, sour and bitter were originally elevated in many patients. Gustatory impairment increased especially with chemo- and radiotherapy. Recovery, however, took place within a year to almost original levels. Salivation was originally not impaired. Resting salivary flow rate (SFR) of the combined therapy group was decreased to half the initial rate, and a 20% decrease of SFR was seen in the PLM group. Corresponding to SFR, 99mTc uptake of the submandibular glands had declined, and salivary viscosity had increased. Salivary gland damage persisted during the study, and appeared irreversible. It was concluded from these results that taste impairment by oral cancer treatment is temporary, while damage to the salivary glands is permanent.

Adult↗
PubMed2000

Effects of oral clonidine premedication on side effects of intravenous ketamine anesthesia: a randomized, double-blind, placebo-controlled study.

STUDY OBJECTIVE: To determine the effects of oral clonidine premedication on hemodynamic changes during the entire course of ketamine anesthesia and incidence of postoperative adverse reactions. DESIGN: Randomized, prospective, double-blind, placebo-controlled study. SETTING: Department of Anesthesiology, University of Tsukuba Hospital, Ibaraki, Japan. PATIENTS: 39 ASA physical status I and II patients undergoing superficial surgeries. INTERVENTIONS: Placebo, clonidine 2.5 micrograms/kg, and clonidine 5 micrograms/kg groups received respective doses of oral clonidine 90 minutes prior to surgery. Anesthesia was induced with ketamine 2 mg/kg intravenously (i.v.), trachea was intubated, and anesthesia was maintained with 67% nitrous oxide, oxygen, and supplemental ketamine (1 mg/kg) when systolic blood pressure and heart rate (HR) exceeded 180 mmHg and 100 bpm, respectively. MEASUREMENTS AND MAIN RESULTS: In the clonidine 2.5 micrograms/kg group, HR response to tracheal intubation was significantly less, while in the clonidine 5 micrograms/kg group both mean arterial pressure and HR responses were significantly suppressed, compared with the placebo group. Intraoperative coefficients of variations of HR were significantly less in both clonidine groups than the placebo group. Incidence of nightmare and degree of salivation were significantly less in the clonidine 5 micrograms/kg group than in the placebo group. CONCLUSION: Oral clonidine 2.5 micrograms/kg and clonidine 5 micrograms/kg attenuates cardiostimulatory effects, while clonidine 5 micrograms/kg was associated with reduced incidence and severity of nightmare and salivation attributable to i.v. ketamine.

Administration, Oral↗
PubMed1997

Quantitative evaluation of opioid withdrawal signs in rats repeatedly treated with morphine and injected with naloxone, in the absence or presence of the antiabstinence agent clonidine.

An opioid withdrawal syndrome was induced in rats by repeated morphine administration and final naloxone injection. The withdrawal causes alteration of several physiological signs. The aim of the study was to describe a quantitative opioid abstinence syndrome to validate the methodology by utilizing clonidine, a well-known antiwithdrawal agent, and propose the procedure for the screening of antiabstinence drugs. In particular, rats were treated with saline, morphine, naloxone, morphine and naloxone and four doses of clonidine (0, 0.04, 0.1, and 0.25 mg/kg orally). In rats repeatedly exposed to morphine and then injected with naloxone, signs like excretion of feces and urine, salivation, behavioral jumping and wet dog shakes, rectal temperature, and pain threshold have been observed. Consequently, the objective symptoms observed in morphine plus naloxone-treated animals have been taken as markers of opioid withdrawal. These factors have been quantitatively measured and grouped to form a standardized procedure of opioid abstinence syndrome. In addition, it is possible to observe that the antiabstinence drug clonidine exerted effects on modified physiological signs appearing in morphine-dependent rats treated with naloxone, like fecal excretion, levels of rectal temperature, latency times, salivation as well as jumping behavior. The effects exerted by clonidine in this procedure and in other methods are compared and appear to be similar. In addition, comparative observations referring to both the previous methods and the present procedure related to the type of signs studied, the modality of evaluation, and suppressive activity exerted by the antiwithdrawal agent, clonidine, are performed: the greater accuracy of the proposed method becomes apparent. Thus, this experimental model, validated by the antiabstinence agent clonidine, is proposed as a useful screen for drugs affecting opioid withdrawal syndrome.

Administration, Oral↗
PubMed1983

In vitro feeding of Dermacentor andersoni (Stiles): effects of histamine and other mediators.

Female Dermacentor andersoni were induced to feed on defibrinated bovine blood through fixed mouse skin membranes. Their feeding behaviour was recorded electronically, the tick being incorporated into the circuit and acting as a variable resistor during the periods of sucking, salivation and rest. Recordings of the feeding behaviour of these ticks were similar to those of ticks feeding on rabbits. Known concentrations of histamine, serotonin, dopamine, prostaglandin E1 and prostaglandin F2a were added singly or in combination to the feeding medium of ticks attached to the mouse skin membrane. Addition of both histamine and serotonin was followed by a significant reduction in the amplitude or recordings associated with sucking and salivation. The concentration of mediators producing this effect was less than 10 mM, a concentration comparable to that of histamine found locally in the skin of tick-resistant guinea-pigs. Comparisons are made between the effects produced by these mediators in ticks and the effects of serotonin and other amines known to produce modulation of complex behaviour patterns in other invertebrates.

Animals↗
PubMed2005

Alterations in behavioral responses to a cholinergic agonist in post-pubertal rats with neonatal ventral hippocampal lesions: relationship to changes in muscarinic receptor levels.

Excitotoxic neonatal ventral hippocampal (NVH) lesion in rats is considered as a putative animal model of schizophrenia as lesioned animals show characteristic post-pubertal emergence of neurochemical and behavioral abnormalities analogous to some of those seen in this disease. Converging evidence points to the involvement of central cholinergic system in this neuropsychiatric disorder, and our previous studies have suggested that cholinergic neurotransmission may be altered in post-pubertal NVH lesioned rats. We investigated here muscarinic receptor reactivity in NVH lesioned animals by measuring the effects of the muscarinic receptor agonist oxotremorine on physiological responses known to be modulated by these receptors such as body temperature, salivation, tremor, pain, and prepulse inhibition of the acoustic startle (PPI). Quantitative receptor autoradiography revealed that post-pubertal NVH lesioned animals display increased levels of [3H]pirenzepine/M1-like and [3H]AFDX-384/M2-like receptor binding sites in the striatum, nucleus accumbens, and in subareas of the dorsal hippocampus. Moreover, in response to the systemic administration of oxotremorine (0.25 mg/kg), post-pubertal NVH lesioned rats exhibited increases in salivation and tremor, and a greater reduction in body temperature compared to sham control animals. Increases in the hot-plate latency were also observed suggesting enhanced antinociceptive effects of oxotremorine in post-pubertal NVH lesioned animals. Finally, oxotremorine (0.1 and 0.25 mg/kg) disrupted PPI in post-pubertal sham control rats while the muscarinic receptor antagonist biperiden (0.5 and 1.0 mg/kg) normalized this behavior in NVH lesioned rats. Taken together, these findings reveal that post-pubertal NVH lesioned rats display enhanced muscarinic receptor responsiveness, which may relate to some behavioral abnormalities reported in this animal model.

Analgesics↗
PubMed1987

Is there neural control over electrolyte reabsorption in the human salivary gland?

A study was made of changes induced by cholinergic agonists and antagonists in the K+, Na+, Ca2+ and Cl- content of saliva of 22 human subjects with denervated parotid salivary glands. At all stages after denervation there was an increased content of Na+ and Cl- in the secretion of the denervated gland as compared with that of the control glands: after administration of pilocarpine and carbacholine; after administration of a combination of atropine and pilocarpine; in 'paradoxical' salivation induced by atropine, scopolamine, metacine or chlorosyle; in spontaneous secretion; in reflex secretion when this was partially restored. The concentrations of Na+ and Cl- in the secretion of the denervated gland were disproportionately higher than would have been expected from the raised salivation rate. Secretions from the denervated glands by virtue of their increased content of Na+ and Cl- resembled so-called primary saliva. The increased output of Na+ and Cl- and high concentrations of these ions in the secondary saliva after denervation indicates that there is loss of the normal neural control over reabsorption of electrolytes in the epithelium of the glandular ducts. Further, that absence of this control results in disturbances of membrane ionic transport, of membrane permeability and of the metabolism of the gland.

Autonomic Nervous System↗
PubMed2001

Comparison of clozapine and haloperidol on some autonomic and psychomotor functions, and on serum prolactin concentration, in healthy subjects.

AIMS: To compare the autonomic, neuroendocrine and psychomotor effects of single doses of the 'atypical' antipsychotic clozapine and the 'classical' antipsychotic haloperidol, in healthy male volunteers. METHODS: Clozapine (50 mg), haloperidol (3 mg) and placebo were administered to 12 healthy male volunteers at weekly intervals, according to a balanced double-blind design. Resting pupil diameter, salivary output, heart rate, blood pressure, plasma prolactin concentration, critical flicker fusion frequency and subjective 'alertness', 'contentedness' and 'anxiety' were measured at baseline and 2, 3, 4 and 5 h after drug ingestion. Data were analysed by analysis of variance with individual comparisons (Dunnett's test) with a significance criterion of P < 0.05. RESULTS: Significant treatment effects (difference from placebo [mean, 95% CI] 5 h after drug ingestion) were as follows: clozapine reduced pupil diameter (mm; -3.02 [-3.56, -2.47]), salivary output (g; -0.34 [-0.60, -0.08]), mean arterial blood pressure (mm Hg; -8.7 [-14.3, -3.1]), critical flicker fusion frequency (Hz; -3.26 [-3.94, -2.58]), and subjectively-rated 'alertness' (mm; -20.94 [-29.21, -12.67]) and 'contentedness' (mm; -12.98 [-17.90, -8.06]), whereas haloperidol increased prolactin concentration (mU l(-1); 301.3 [196.7, 405.8]) and caused small reductions in pupil diameter (mm; -0.68 [-1.23, -0.14]), mean arterial blood pressure (mm Hg; -7.0 [-12.6, -1.4]) and critical flicker fusion frequency (Hz; -1.15 [-1.83, -0.47]). CONCLUSIONS: The effects of the antipsychotics are in agreement with their receptor binding profiles: alpha(1)-adrenoceptor blockade by clozapine may contribute to reductions in pupil diameter, salivation, mean arterial blood pressure and sedation, and muscarinic cholinoceptor blockade by the drug may underlie the reduction in salivation. Conversely, D(2) dopamine receptor blockade by haloperidol is likely to be responsible for the increase in prolactin secretion evoked by the drug.

Adult↗
PubMed1998

Salivary secretion: stimulatory effects of chewing-gum versus paraffin tablets.

Paraffin tablets are commonly used in clinical saliva tests whereas chewing-gum is recommended to increase salivation in xerostomic patients. The aim of this study was to compare the effect on salivation of these stimuli. Saliva stimulated by chewing-gum or paraffin tablets was sampled on separate occasions from eight healthy subjects (25-45 yr). Whole or parotid saliva were collected for 6 min (1 min + 5 min) and 21 min (1 min + 5 min x 4), respectively. pH of saliva was measured with and without the addition of HC1 (titrated pH). Total parotid protein was measured using the microBSA-assay. Initially, flow rates were significantly higher during the chewing of gum vs. paraffin tablets (whole saliva 5.18 vs. 2.99 ml/min, parotid saliva 0.83 vs. 0.42 ml/min). Conversely, during final chewing periods, parotid flow rates, pH, and titrated pH were significantly higher during paraffin chewing. When comparing the stimuli, parotid protein output was higher initially during gum chewing, but in the final period paraffin chewing elicited the higher output. It was concluded that the clinical test of paraffin chewing gives a good estimate of the expected whole saliva response to chewing-gum. Furthermore, extended chewing of paraffin tablets seemed to influence parameters of parotid saliva positively.

Adult↗
PubMed1999

Comparison of the effects of venlafaxine, desipramine, and paroxetine on noradrenaline- and methoxamine-evoked constriction of the dorsal hand vein.

AIMS: To examine whether the antidepressant venlafaxine, a novel serotonin-noradrenaline re-uptake inhibitor (SNRI), can modify alpha-adrenoceptor-mediated venoconstriction in man. The effects of venlafaxine were compared with those of desipramine, a tricyclic antidepressant with noradrenaline uptake inhibiting properties, and paroxetine, a selective serotonin re-uptake inhibitor (SSRI), on noradrenaline-and methoxamine-evoked venoconstriction using the dorsal hand vein compliance technique. METHODS: Fifteen healthy male volunteers participated in five weekly experimental sessions. Each session was associated with a clinically effective dose of an antidepressant or placebo. The following oral dosages were used: venlafaxine 75 mg, venlafaxine 150 mg, desipramine 100 mg, paroxetine 20 mg, or placebo. A double-blind, cross-over, balanced design was used. In each session, dose-response curves to both locally infused noradrenaline acid tartrate (0.1-33.33 ng min-1 ) and methoxamine hydrochloride (0.5-121.5 microg min-1 ) were constructed. Systolic and diastolic blood pressure and pulse rate were measured in the supine and erect positions. Salivation was measured by the dental roll technique. RESULTS: Venlafaxine 150 mg and desipramine 100 mg potentiated the venoconstrictor response to noradrenaline (anova of log ED50s: P<0.01; individual comparisons: venlafaxine 150 mg vs placebo: P<0.005; mean difference, 95% CI: -0. 49 (-0.81, -0.17); desipramine 100 mg vs placebo: P<0.005; mean difference, 95% CI: -0.34 (-0.60, -0.09) without affecting the response to methoxamine. Neither paroxetine nor placebo had any effects on the venoconstrictor responses. Both doses of venlafaxine increased systolic blood pressure (supine and erect) and venlafaxine 150 mg increased diastolic blood pressure (supine) (anova, P<0.05). Desipramine increased heart rate (P<0.05). Desipramine and both doses of venlafaxine reduced salivation (P<0.025). CONCLUSIONS: These results show that, similarly to desipramine 100 mg, venlafaxine 150 mg can potentiate venoconstrictor responses to noradrenaline, consistent with venlafaxine's ability to block noradrenaline uptake in man. The importance of noradrenaline uptake blockade in these observations is confirmed by the lack of effect of the antidepressants on methoxamine-evoked venoconstriction and the failure of paroxetine to modify noradrenaline-evoked venoconstriction.

Adrenergic alpha-Agonists↗
PubMed2001

Syndromes with salivary dysfunction predispose to tooth wear: Case reports of congenital dysfunction of major salivary glands, Prader-Willi, congenital rubella, and Sjögren's syndromes.

Four cases-of congenital dysfunction of the major salivary glands as well as of Prader-Willi, congenital rubella, and Sjögren's syndromes-were identified in a series of 500 patients referred for excessive tooth wear. Although there was evidence of consumption of highly acidic drinks, some occlusal parafunction, and unacceptable toothbrushing habits, salivary dysfunction was the salient factor predisposing a patient to tooth wear in these syndromal cases. The 500 subjects have been characterized either as having medical conditions and medications that predispose them to xerostomia or lifestyles in which workplace- and sports-related dehydration lead to reduced salivary flow. Normal salivation, by buffering capacity, clearance by swallowing, pellicle formation, and capacity for remineralization of demineralized enamel, protects the teeth from extrinsic and intrinsic acids that initiate dental erosion. Thus, the syndromes, unrelated in many respects, underline the importance of normal salivation in the protection of teeth against tooth wear by erosion, attrition, and abrasion.

Adult↗
PubMed1981

Impaired salivary gland secretory function following the induction of rapid, synchronous vitamin A deficiency in rats.

Rapid and essentially synchronous vitamin A deficiency was induced by the withdrawal of retinoic acid from stringently deficient animals reared by feeding early weight plateau vitamin A-deprived male rats diets first supplemented with and then lacking in 2 micrograms retinoic acid/g diet in repeating 18:10 day cycles. Secondary inanition was minimized by the control led force-feeding of deficient and control animals. The time to inset of pilocarpine (3 mg/kg body weight) induced salivation increased progressively starting 6-8 days after retionate withdrawal. Concomitantly, saliva volumes in the 20 minutes following the onset of salivation decreased. Protein and alpha-amylase concentrations were constant until around days 10-12 (T10-12) of deficiency but then decreased. Synthesis of proteins was normal, however as judged by total parotid gland alpha-amylase activity (T14). Seemingly, vitamin A deficiency may directly affect cells involved in saliva secretion, since decreased secretory function was noted several days prior to keratinization and blockage of the striated and excretory ducts.

Animals↗
PubMed1999

Treatment of xerostomia with the bile secretion-stimulating drug anethole trithione: a clinical trial.

BACKGROUND: Saliva protects the oral mucosa, inhibiting microbial overgrowth. Hyposalivation, therefore, induces multiple oral disorders, although treatment of hyposalivation is very difficult. METHODS: A cholagogue, anethole trithione (AT) was administered to patients with symptomatic hyposalivation (xerostomia) caused by senile hypofunction (4 men and 17 women; senile group), medications (6 men and 17 women; drug group), and oral cancer therapy (two men and three women; cancer group). For control groups, an artificial saliva was administered to 45 patients consisting of senile hypofunction (10 men and 16 women), drug-induced xerostomia (3 men and 10 women) and oral cancer therapy-induced xerostomia (four men and two women). RESULTS: Two weeks after administration of AT (6 tablets per day), both nonstimulated salivary flow rate (SFR) and stimulated SFR increased in a statistically significantly manner from 0.76 +/- 0.41 and 5.18 +/- 3.02 to 1.54 +/- 1.33 (P<0.05) and 9.07 +/- 4.10 mL/10 min (P<0.05), respectively. Of the three groups, the drug group showed the largest increases in both SFRs, from 0.90 +/- 0.54 and 6.29 +/- 4.12 to 1.69 +/- 1.65 and 12.09 +/- 5.10 mL/10 min (P<0.05 and P<0.02, respectively). Patients in the control group had almost constant SFRs. After AT administration, the salivary viscosity was, however, mildly decreased and concentrations of secretory-immunoglobulin A, lactoferrin, potassium, and chloride in nonstimulated saliva were almost constant. Corresponding with the increase of salivation, oral discomfort and inflammation were improved or resolved in 41 patients of the AT group within about 4 weeks, whereas improvement was observed in only nine patients of the control group. CONCLUSIONS: These results indicate that AT sufficiently stimulates salivation and improves xerostomia.

Adult↗
PubMed2000

Comparison of central and peripheral pharmacologic effects of biperiden and trihexyphenidyl in human volunteers.

In this double-blind, randomized study, indices of central (memory, sedation) and peripheral (salivation, ratio of R-R interval on electrocardiogram) muscarinic function were evaluated in 14 healthy volunteers who received trihexyphenidyl, biperiden, and placebo. Additionally, serum drug levels were obtained 2 hours after oral administration. All subjects participated in three study sessions. During each session, subjects received two doses of biperiden (4 mg), trihexyphenidyl (5 mg), or placebo, and four series of tests were administered. The tests included the determination of cardiac response to standing (R-R ratio), mouth salivation, finger-tapping speed, digit span (forward and backward), a selective reminding task, and visual analog scales (VAS). On the VAS, subjects rated biperiden as significantly more sedating than either trihexyphenidyl or placebo, and both biperiden and trihexyphenidyl were associated with more dizziness than was placebo. Saliva production was significantly reduced by both trihexyphenidyl and biperiden compared with placebo. Digit span performance was significantly decreased in only the backward direction. The selective reminding task revealed highly significant decrements in the number of words recalled and consistent long-term retrieval after both biperiden and trihexyphenidyl. Delayed recall was significantly decreased by both active drugs. Both trihexyphenidyl and biperiden caused a significant increase in the R-R ratio comparison with placebo. With the exception of the VAS measurement of sedation, the effects caused by biperiden and trihexyphenidyl did not differ. The results of this study do not support the hypothesis that the side effect profile of biperiden is significantly different from that of trihexyphenidyl.

Adolescent↗
PubMed1996

Determination of the efficacy of topical oral pilocarpine for postirradiation xerostomia in patients with head and neck carcinoma.

Pilocarpine hydrochloride suspended in a candy-like pastille was evaluated as a topical treatment for radiation-induced xerostomia in head and neck cancer patients. This local delivery system, which differs from systemically administered pilocarpine preparations, was developed to hopefully maximize the local response and minimize the systemic side effects. A prospective, randomized, double-blind, placebo-controlled trial was undertaken to determine objective and subjective efficacy in reversing the decrease in salivation. Forty previously irradiated patients received increasingly higher pilocarpine dosages in pastilles for 5 successive weeks. At each successive dose of pilocarpine, no significant increased salivation was noted. However, 25 (74%) of 34 patients reported that pilocarpine alleviated their subjective xerostomia. Topical pilocarpine administration has shown similar results to previous systemic delivery methods for radiation-induced xerostomia, but with improved patient tolerance.

Administration, Oral↗
PubMed1995

Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide after intravenous and oral administration to healthy volunteers: relationship to nonanalgesic actions.

Healthy volunteers were given morphine as an i.v. infusion (10 mg), immediate release (IR) tablets (3 x 10 mg), and as a new controlled release (CR) tablet (30 mg) on separate occasions. Venous blood samples were analyzed for morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) using high-performance liquid chromatography (HPLC). Pupil size, salivation, and central nervous system (CNS) effects were evaluated serially. Pharmacokinetic parameters, calculated using a two-compartment model, were in accordance with previous results for i.v. administration of morphine. The absolute bioavailability of morphine in both IR and in CR tablets was, 32%, and the relative bioavailability of the CR tablet versus the IR tablets was 103% (91-115%, 95% confidence interval). Pupil size and unstimulated saliva production were significantly reduced and CNS effects most pronounced following i.v. infusion of morphine, but were only moderately affected after oral administration with IR or CR tablets. Miosis and reduction of salivation were observed at moderate concentrations of morphine and M6G. A pharmacokinetic/pharmacodynamic model based on previous studies of receptor binding and potency of morphine and its metabolites was used to assess the concentration-effect relationships. According to this model, M6G was four and eight times more potent than morphine in producing miosis and reduction of saliva production, respectively. The same model indicated that intrinsic activities of M6G and morphine were similar for both effect parameters, whereas M3G was either inactive or even opposed the effects of morphine and M6G.

Administration, Oral↗
PubMed1987

Effects of triprolidine and dipipanone in the cold induced pain test, and the central nervous system of healthy volunteers.

1 Twelve healthy volunteers took part in a study of the interaction between the antihistamine triprolidine and the opioid dipipanone in the cold induced pain (CP) test and tests of sedation. They received placebo, triprolidine 2.5 mg, dipipanone 8 mg or the combination of the two active treatments according to a double-blind, randomised, balanced, crossover design. 2 Antihistamine activity was demonstrated by triprolidine reducing the size of wheals and flares produced by intradermal histamine 1.6 micrograms. However, triprolidine produced no analgesia in the CP test, nor did it enhance the analgesia produced by dipipanone alone. 3 Neither treatment alone produced statistically significant sedation, assessed by visual analogue scales (VAS), side effect check list, body sway and reaction times. However, the combination did cause significant sedation. 4 Dipipanone reduced pupil size, depressed respiration, and decreased salivation. Triprolidine had no effects on pupil size and respiration, but reduced salivation slightly. It was concluded that histaminergic (H1) mechanisms are unlikely to be involved in pain produced by cold.

Adult↗