Effects of An-Shen-Bu-Nao Syrup on the inducible nitric-oxide synthase activity and melatonin in brain of sleep deprivation rats

Objective： To study the effects of An-Shen-Bu-Nao Syrup （AS） on the inducible nitricoxide synthase （iNOS） activity and melatonin content in brain of sleep deprivation （SD） rats. Methods： Rats were divided into groups of control, SD model, SD＋AS （0.02ml/kg）, and SD＋ AS （0.06ml/kg） . The rats were fed with AS for 2 weeks and were subjected to sleep deprivation for 4 days, and then the iNOS activity in the front cortex was analyzed, and melatonin in the pineal gland was analyzed with HPLC. Results： Compared with the control rats, SD rats had the significantly elevated iNOS activity in the front cortex. Rats treated with AS （0. 06ml/kg） showed significantly decreased iNOS activity than SD rats.     

Effects of cysteine on the pharmacokinetics of docetaxel in rats with protein–calorie malnutrition

1. The objective of this study is to report the effects of cysteine on the pharmacokinetics of intravenous and oral docetaxel in rats with protein–calorie malnutrition (PCM). The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of docetaxel were assessed using control, CC (control with cysteine), PCM and PCMC (PCM with cysteine) rats. The effects of cysteine on the intestinal absorption of docetaxel were further investigated through in vitro transport studies using rat intestine and Caco-2 cell monolayers.

2. The AUCs (the areas under the plasma concentration-time curve from time zero to time infinity) of intravenous docetaxel in PCM rats were significantly greater than in the control rats because of the significant decrease in the hepatic CYP3A. In PCMC rats, the elevated AUCs in PCM rats returned to control levels. The AUC_{0–6 h}s of oral docetaxel in PCM rats were significantly smaller than that in the control rats, mainly due to the decrease in gastrointestinal absorption. In CC and PCMC rats, oral cysteine supplement enhanced the gastrointestinal absorption of docetaxel probably via intestinal P-gp inhibition.

3. If the present rat data could be expressed to humans, the alterations in docetaxel absorption and metabolism should be considered in designing a dosage regimen for cancer patients with PCM state after cysteine supplement.

     

Subjective sleep–wake parameters in treatment-seeking opiate addicts

We investigated subjective sleep parameters and sleep difficulties of opiate addicts undertaking methadone detoxification and identified their sleep profile. Using the St Mary's Sleep Questionnaire, we compared the subjective sleep parameters of 27 consecutively consenting patients (16 males, 11 females) with a mean age of 33 years (S.D.=7.5) undertaking in-patient methadone detoxification with those of 26 drug-free controls (9 males, 17 females) with a mean age of 35 years (S.D.=8.0). Our findings reveal that subjective sleep parameters of opiate addicts and controls are quantitatively and qualitatively different. The patients are more likely than controls to report difficulty initiating sleep (OR=5.42; 95%CI=1.43, 20.47); difficulty maintaining sleep (OR=16.50; 95%CI=3.81, 71.47); inadequate sleep quality (OR =8.56; 95%CI =2.04, 35.81); and inadequate sleep quantity (OR=9.00; 95%CI=2.49, 32.57).     

Acute administration of the novel serotonin and noradrenaline reuptake inhibitor,S33005, markedly modifies sleep–wake cycle architecture in the rat

Rationale The interrelationship between depressive states and sleep–wake cycle architecture is characterised by a decreased latency to the first paradoxical sleep (PS) episode, together with an enhancement of PS during the first part of the night. Conversely, slow-wave sleep (SWS) is decreased and intermittent awakenings increased. Notably, antidepressant treatment is generally associated with a diminution of PS. Objectives In light of these observations, we examined the influence of acute administration of the novel mixed serotonin-noradrenaline reuptake blocker, (−)1-(1-dimethylaminomethyl 5-methoxybenzocyclobutan-1-yl)-cyclohexanol HCl (S33005), upon sleep–wake architecture in rats. Methods Animals were injected with vehicle or incremental doses of S33005 at the onset of either the dark or light periods. Digitised polygraphic recordings were performed, and changes evoked by S33005 were determined over 24-h recording periods, i.e., number and duration of sleep–wake episodes, latencies to PS and SWS, power band spectra of the electroencephalogram (EEG) and circadian changes. Results At 0.04 mg/kg, S33005 was inactive, whereas at 0.63 mg/kg, it modestly increased PS latencies and diminished PS duration during the light period. At 10 mg/kg, S33005 reduced markedly PS duration for about 4-h when injected prior to both light and dark periods. Latency to PS was prolonged, and the circadian acrophase was delayed. These effects are in keeping with previous studies of monoamine reuptake inhibitors, but, notably, SWS duration was increased when S33005 was injected at the onset of the light phase (+4%). These changes occurred without marked modifications in circadian rhythmicity or EEG spectral band power. Finally, even at the highest dose of S33005, only a limited rebound of SWS (+5%) and PS (+10%) was apparent. Amongst antidepressant to date examined, this is an original profile of influence upon sleep patterns. Conclusions These results demonstrate a pattern of influence of S33005 upon sleep–wake architecture in rats which is globally consistent with antidepressant properties, but with a distinctive enhancement of restorative slow-wave sleep.     

Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist,agomelatine, on the rat sleep–wake cycle architecture

Rationale  The novel antidepressant, agomelatine, behaves as an agonist at melatonin MT₁ and MT₂ receptors and as an antagonist at serotonin (5-HT)_2C receptors. In animal models and clinical trials, agomelatine displays antidepressant properties and re-synchronizes disrupted circadian rhythms. Objectives  The objectives of this study were to compare the influence of agomelatine upon sleep–wake states to the selective melatonin agonists, melatonin and ramelteon, and to the selective 5-HT_2C receptor antagonist, S32006. Methods  Rats were administered with vehicle, agomelatine, ramelteon, melatonin, or S32006, at the onset of either dark or light periods. Polygraphic recordings were performed and changes determined over 24 h, i.e., number and duration of sleep–wake episodes, latencies to rapid eye movement (REM) and slow-wave (SWS) sleep, power band spectra of the electroencephalogram (EEG), and circadian changes. Results  Administered at light phase onset, no changes were induced by agomelatine. In contrast, administered shortly before dark phase, agomelatine (10 and 40 mg/kg, per os) enhanced duration of REM and SWS sleep and decreased wake state for 3 h. Melatonin (10 mg/kg, per os) induced a transient enhancement in REM sleep followed by a reduction in REM and SWS sleep and an increase in waking. Ramelteon (10 mg/kg, per os) provoked a transient increase in REM sleep. Finally, S32006 (10 mg/kg, intraperitoneally), administered at dark phase onset, mimicked the increased SWS provoked by agomelatine, yet diminished REM sleep. Conclusions  Agomelatine possesses a distinctive EEG profile compared with melatonin, ramelteon, and S32006, possibly reflecting co-joint agonist and antagonist properties at MT₁/MT₂ and 5-HT_2C receptors, respectively. An erratum to this article can be found at     

Influence of the novel antidepressant and melatonin agonist/serotonin2C receptor antagonist,agomelatine, on the rat sleep–wake cycle architecture

Rationale  Behavioral and dopamine responses to cocaine are sexually dimorphic: Female rats exhibit higher levels of locomotor and reward-associated behaviors after cocaine administration and dopamine release than do males. Activation of the dopamine- and cAMP-regulated phosphoprotein of Mr 32 kDa (DARPP-32) intracellular cascade mediates responses to cocaine. Objective  To examine the possibility that acute cocaine administration alters the DARPP-32 cascade in a sexually dimorphic pattern. Materials and methods  Male and female rats received either saline or cocaine (30 mg/kg). Protein levels of DARPP-32, phosphorylation of DARPP-32 at the Thr34 site (P-Thr34-DARPP-32), protein phosphatase 1 (PP-1), and protein phosphatase 2B (PP-2B) in nucleus accumbens were measured via Western blot analysis. Results  Females had higher protein levels of DARPP-32, P-Thr34-DARPP-32, calcineurin A (CaN-A; catalytic subunit of PP-2B), and calcineurin B (CaN-B; regulatory subunit of PP-2B) than males 5 min after saline treatment. In females, CaN-A protein levels were also higher at 15 min and PP-1 protein levels were higher 30 min after saline administration than males. In male rats, cocaine significantly increased CaN-A protein levels at 30 min and CaN-B protein levels at 15 min. In females, cocaine administration significantly decreased protein levels of DARPP-32, P-Thr34-DARPP-32, and CaN-A at 45 min but increased PP-1 protein levels at 30 min. Overall, males had higher activation of the DARPP-32 pathway after cocaine administration than did females. Conclusion  These novel results show that basal and cocaine-induced sex differences in the DARPP-32/PP-1 cascade may be responsible for the sexual dimorphism in acute cocaine-induced behavioral responses.     

Effects of garlic extract on TNF-α expression and oxidative stress status in the kidneys of rats with STZ + nicotinamide-induced diabetes

Context: Allium sativum L. (Liliaceae) (garlic) is a medicinal plant that is widely used in herbal medicine. Nephropathy is a complication of diabetes that is induced by long-term hyperglycaemia.

Objective: The effects of aqueous extract of garlic (AGE) on the expression of tumour necrosis factor-alpha (TNF-α) and oxidative stress status were studied in the kidneys of rats with streptozotocin (STZ)?+?nicotinamide-induced diabetes.

Materials and methods: Twenty-four Wistar rats were divided into four groups: control rats, rats with STZ?+?nicotinamide-induced diabetes that received a single dose of STZ (65?mg/kg) and nicotinamide (110?mg/kg) intraperitoneally, diabetic rats that were treated with garlic (2?g/kg/d, gavage), and normal rats that received garlic (2?g/kg/d, gavage). The glucose level was determined in the start of study, 7 d after induction of diabetes and 33 d after treatment with garlic. At the end of the treatment period, urea, uric acid and creatinine levels were estimated in sera. Malondialdehyde (MDA), total oxidant status (TOS), nitric oxide (NO) levels and TNF-α gene and protein expression were measured in the renal tissues of the rats.

Results: The glucose, uric acid, and urea levels increased in the serum of diabetic rats compared with control rats, and decreased in garlic-treated diabetic rats compared with diabetic rats (p?p?p?p?p?Discussion and conclusion: These results indicate that garlic extract has hypoglycaemic, antioxidant and anti-inflammatory properties; therefore, it can be useful for the alleviation of diabetic complications.     

Effects of rosiglitazone on native low-density-lipoprotein-induced respiratory burst in circulating monocytes and on the leukocyte–endothelial interaction in cholesterol-fed rats

Low-density lipoprotein (LDL) has been implicated in the initiation and progression of atherosclerotic vascular disease. But whether LDL can elicit similar effects in the microcirculation remain unexplored. To approach this issue, the hypothesis that LDL promotes oxidative stress in monocytes and results in microvascular inflammation was tested. Native LDL was capable of stimulating respiratory burst in rat monocytes, and this was blocked by BAPTA, cytochalasin B, apocynin, and diphenyliodonium. In monocytes from rats on a high-cholesterol (4%) diet, increased intracellular calcium, actin polymerization, respiratory burst, and surface CD18 expression were found. Concurrently, leukocyte–endothelial interaction was enhanced in the cremaster microcirculation. Rosiglitazone, an insulin-sensitizing agent with antiinflammatory properties, was found to suppress native-LDL-induced actin polymerization and respiratory burst in monocytes. It also improved leukocytes activation and leukocyte–endothelial interaction due to the high cholesterol intake. Hence, native LDL stimulation of monocytes contributed to hypercholesterolemia-associated microvascular inflammation, which could be treated by rosiglitazone.     

Antiosteoporotic activity of Du–Zhong–Wan water extract in ovariectomized rats

Context Eucommiae Cortex and Radix Dipsaci, occurring in a ratio of 1:1 in Du-Zhong-Wan (DZW), a Chinese herbal medicine, is available as a water extract followed by ethanol precipitation for the treatment of osteoporosis, fractures and menopausal syndrome.

Objective This study investigates the protective effects of DZW in ovariectomy (OVX)-induced bone loss in a rat osteopenia model.

Materials and methods Sixty Sprague–Dawley rats were randomly divided into the sham-operated group (SHAM) and five OVX subgroups: OVX with vehicle (OVX), 17β-estradiol (E2) and with three graded doses of DZW. Daily oral administration of the different samples started on the fifth week and lasted for 12 weeks, respectively. The body weight, uterus wet weight, serum biochemical parameters, bone mineral density (BMD), bone biomechanical properties, bone microarchitecture and immunohistochemistry were examined.

Results Compared with the SHAM group, the DZW treatment significantly reversed the osteoporotic changes in OVX rats. The DZW-H group showed that serum tartrate-resistant acid phosphatase 5b (TRACP-5b) levels reduced by 152.25% (p?<?0.01) and osteocalein (OCN) levels dose dependently increased by 118.43% (p?<?0.01) as compared with the OVX group. Compared with the OVX group, the DZW at different three dosages of DZW evidently increased the right femur BMD by 112.43, 114.56 and 116.45%, and dramatically promoted bone quality and bone strength (p?<?0.05). Further, immunohistochemical evaluation also showed that DZW administration increased ER expression in uteri (p?<?0.01).

Conclusions DZW exhibits an anti-osteoporotic effect, probably mediated via phyto-estrogenic effects. It might be a potential herbal alternative for the management of postmenopausal osteoporosis.     

Effects of HL-328 on monocrotaline-induced pulmonary hypertension in rats

AIM: To study the effect of HL-328, a plant alkaloid with calcium antagonist action, on monocrotaline(MCT)-induced pulmonary hypertensive rats. METHODS: Male Wistar rats weighing 150-170 g were derided into 6     

Effects of triptolide on pharmacokinetics of amlodipine in rats by using LC–MS/MS

Context: Triptolide and amlodipine are often simultaneously used for reducing urine protein excretion after renal transplantation in China clinics.

Objective: This study investigated the effects of triptolide on the pharmacokinetics of amlodipine in male Sprague–Dawley rats.

Materials and methods: The pharmacokinetics of amlodipine (1?mg/kg) with or without triptolide pre-treatment (2?mg/kg/day for seven?days) were investigated using a sensitive and reliable LC–MS/MS method. Additionally, the inhibitory effects of triptolide on the metabolic stability of amlodipine were investigated using rat liver microsome incubation systems.

Results: The results indicated that when the rats were pre-treated with triptolide, the C_max of amlodipine increased from 13.78?±?3.57 to 19.96?±?4.56?ng/mL (p?T_max increased from 4.04?±?1.15 to 5.89?±?1.64?h (p?AUC_0–t increased by approximately 104% (p?p?Conclusions: In conclusion, these results indicated that triptolide could affect the pharmacokinetics of amlodipine, possibly by inhibiting the metabolism of amlodipine in rat liver when they are co-administered.     

Effects of verapamil on the cardiac α1-adrenoceptor signalling system in diabetic rats

We evaluated the effects of chronic verapamil treatment on the cardiac α₁-adrenoceptor signalling system in streptozocin-induced diabetic rats. The decrease in maximum cell surface [³H]bunazosin binding (B_max) in isolated cardiac myocytes from the diabetic group (−46%, P < 0.01) was completely reversed by a 4-week course of verapamil, while B_max in the verapamil-treated control group was unchanged. Similarly, the reduction in ventricular inositol 1,4,5-trisphosphate (IP₃) production after stimulation with 10 μM noradrenaline (NA) seen in diabetes (−30%, P < 0.01) was completely normalized by verapamil, while the response in the verapamil-treated control group was unaffected. These results indicate that verapamil can induce complete recovery of the impaired cardiac α₁-adrenoceptor signalling system in the diabetic heart without affecting glucose metabolism.     

Effects of peptidase inhibitors on anti-nociceptive action of dynorphin-(1–8) in rats

Previous in vitro studies showed that the degradation of dynorphin-(1-8) [dyn-(1-8)] by cerebral membrane preparations is almost completely prevented by a mixture of three peptidase inhibitors (PIs), amastatin, captopril and phosphoramidon. In the present investigations, effects of the three PIs on the anti-nociception induced by the intra-third-ventricular (i.t.v.) administration of dyn-(1-8) were examined. The inhibitory effect of dyn-(1-8) on the tail-flick response was increased more than 100-fold by the i.t.v. pretreatment of rats with the three PIs. The inhibition produced by dyn-(1-8) in rats pretreated with any combination of two PIs was significantly smaller than that in rats pretreated with three PIs, indicating that any residual single peptidase could inactivate significant amounts of dyn-(1-8). The antagonistic effectiveness of naloxone, a relatively selective mu-opioid antagonist, indicates that dyn-(1-8)-induced inhibition of tail-flick response in rats pretreated with three PIs is mediated by mu-opioid receptors. Furthermore, mu-receptor-mediated inhibition induced by dyn-(1-8) was significantly greater than that produced by [Met5]-enkephalin in rats pretreated with three PIs. The data obtained in the present investigations together with those obtained in previous studies strongly indicate that dyn-(1-8) not only has well-known kappa-agonist activity but also has high mu-agonist activity.     

Effects of the serotonergic agonist mCPP on male rats in the quinpirole sensitization model of obsessive–compulsive disorder (OCD)

Rationale

The serotonergic agonist, meta-chlorophenylpiperazine (mCPP), produces inconsistent effects on obsessive–compulsive disorder (OCD) symptoms, perhaps because clinical studies have not utilized a homogenous OCD subgroup of patients.

Objectives

This study aimed to evaluate mCPP effects on functional components of compulsive checking, using the quinpirole sensitization rat model of OCD.

Methods

In study 1, the effects of mCPP were evaluated in quinpirole rats with compulsive checking. Two experimental groups were co-injected with quinpirole (0.125 mg/kg) and mCPP (0.625 or 1.25 mg/kg), while one control group was co-injected with quinpirole (0.125 mg/kg) and saline and the other control group received co-injections of saline. In study 2, mCPP (0, 0.3125, 0.625, and 1.25 mg/kg) was administered repeatedly to naïve rats and induction of compulsive checking evaluated.

Results

mCPP significantly attenuated quinpirole-induced compulsive checking behavior by reducing vigor of checking (indexed by frequency of checking and length of check) and increasing rest after a bout of checking (indexed by time to the next checking bout), but it did not affect focus on the task of checking (indexed by recurrence time of checking and number of stops before returning to check). In naïve rats, mCPP did not induce compulsive behavior, but the highest dose reduced vigor of checking performance compared to saline controls.

Conclusions

mCPP did not exacerbate or induce compulsive checking behavior. Instead, it ameliorated compulsive checking by reducing vigor of checking and increasing post-checking satiety, without affecting focus on checking. Ameliorative effects of mCPP may involve 5HT_2A/2C receptors in substantia nigra pars reticulata that inhibit expression of motor vigor.     

Effects of theβ-adrenoceptor antagonists acebutolol and metoprolol on sleep pattern in normal subjects

Summary The effects of acute introduction and withdrawal of 2 new -adrenergic blockers, acebutolol and metoprolol, on sleep in normal subjects were investigated. Both the subjective effects of the drug and EEG sleep variables were determined during a baseline period with placebo and in relation to the drug. The results showed that neither drug had a significant effect on sleep pattern in normal subjects. However, a transient effect on certain sleep parameters was seen on the first night of drug administration, with complete return to baseline, on the following night without any evidence of rebound. Possible mechanisms to explain the central actions of -adrenergic blockers are briefly discussed.     

Effects of some GABA-mimetic drugs on the antinociceptive activity of morphine and β-endorphin in rats

Summary Intracerebroventricular administration of muscimol, a potent GABA-receptor agonist, counteracted the antinociceptive effect of morphine or -endorphin in rats as measured by the tail flick method. Muscimol's activity was reversed by bicuculline. Isoguvacine, another GABA agonist, as well as nipecotic acid and guvacine, two inhibitors of neuronal and glial uptake of GABA, also antagonized morphine's antinociceptive effect. A role of the central GABA-ergic system in mediating opiate antinociception is proposed.This study was supported by C.N.R. grant no. CT 77.01401.04     

Effects of β-adrenoceptor antagonists on anaphylactic hypotension in conscious rats

Anaphylactic shock is sometimes fatal or resistant to therapy in patients treated with propranolol, a nonselective β-adrenoceptor antagonist, against cardiovascular diseases. However, it remains unknown which subtype of β-adrenoceptors, β₁- or β₂-adrenoceptor, is primarily responsible for the detrimental effects of propranolol on anaphylactic hypotension. Effects of β₁- and β₂-adrenoceptor antagonists were therefore determined on the survival rate and systemic hypotension in conscious Sprague–Dawley rats that suffered from anaphylactic shock. Mean arterial pressure and portal venous pressure were simultaneously measured. The control rats showed a decrease in mean arterial pressure and an increase in portal venous pressure, but did not die within 48 h after an injection of ovalbumin antigen. The survival rate of the rats pretreated with propranolol (1 mg/kg; n = 7), the selective β₂-adrenoceptor antagonist ICI 118,551 (0.5 mg/kg; n = 7), or adrenalectomy (n = 7) was significantly smaller than that with the selective β₁-adrenoceptor antagonist atenolol (2 mg/kg; n = 7). However, the changes in mean arterial pressure and portal venous pressure were similar for 10 min after antigen among any groups, although propranolol and atenolol attenuated the antigen-induced increase in heart rate. Furthermore, bolus injections of epinephrine (3 μg/kg) at 3 and 5 min after antigen prevented the death of the atenolol-pretreated rats, but only marginally prolonged the survival rates for the ICI 118,551- or propranolol-pretreated and adrenalectomized rats. In conclusion, in rat anaphylactic shock, inhibition of β₂-adrenoceptor causes more detrimental effects than that of the β₁-adrenoceptor. These β-adrenoceptor antagonists may exert detrimental effects on rat systemic anaphylaxis via inhibiting beneficial actions of catecholamines endogenously released from the adrenal gland.     

Effects of κ-opioid receptor ligands on intracranial self-stimulation in rats

Rationale Elevations in cAMP response element binding protein (CREB) function within the mesolimbic system of rats reduce cocaine reward in place conditioning studies and increase immobility in the forced swim test. Each of these behavioral adaptations can be interpreted as a depressive-like effect (i.e., anhedonia, despair) that may reflect reduced activity of brain reward systems. Furthermore, each effect appears due to increases in CREB-mediated expression of dynorphin, since each is attenuated by intracranial injections of the -opioid receptor antagonist norBNI.Objectives Intracranial self-stimulation (ICSS) studies were conducted in rats to determine whether administration of a -agonist would have depressive-like effects on brain stimulation reward, and whether pretreatment with a -antagonist would attenuate any such effects. Conditions that have depressive effects in people (e.g., drug withdrawal) increase the threshold amounts of stimulation required to sustain ICSS in rats.Methods Sprague-Dawley rats with lateral hypothalamic stimulating electrodes were tested in a curve-shift variant of the ICSS procedure after systemic administration of the -agonist U-69593 alone, the novel -antagonist 5-acetamidinoethylnaltrindole (ANTI) alone, or co-administration of both drugs.Results U-69593 dose dependently increased ICSS thresholds, suggesting that activation of -receptors reduced the rewarding impact of the brain stimulation. ANTI had no effects on its own, but it attenuated increases in ICSS thresholds caused by the agonist.Conclusions These data provide further evidence that stimulation of brain -receptors may trigger certain depressive-like signs, and that antagonists may have efficacy as antidepressants without having reward-related actions of their own.     

Effects of the food contaminant semicarbazide following oral administration in juvenile Sprague–Dawley rats

Semicarbazide (SEM) is an azodicarbonamide by-product present in glass jar packaged foods including babyfoods, in bleaching steps and flour treatment. Experimental data showed SEM acting as osteolathyrogen agent, but few toxicological data are available in susceptible life-stages. This study aimed to evaluate effects of SEM oral administration for 28 days at 0, 40, 75, 140 mg/kg bw day during the juvenile period in Sprague–Dawley rats. Histopatological examinations of: epiphyseal cartilage – potential target of SEM lathyrogen action - testes, ovary, uterus, thyroid, thymus, spleen, adrenals, representative of the main developing organs relevant to juvenile toxicity, and neurobehavioural tests in males, were performed. Mortality at high and mid dose levels and significantly decreased body weight gain were observed in males even at the lowest dose. Lack of mineralization in cartilage at all dose levels was present. Marked alterations of spontaneous motor and exploratory behaviours were evident even at 40 mg/kg. Histological alterations were observed in all tissues; thyroid and ovary effects were present also at 40 mg/kg. The present study indicate that the NOAEL in juvenile rats is lower than 40 mg/kg for SEM oral administration. SEM administration during juvenile period exerted pleiotropic effects and further studies are suggested to elucidate mechanisms.     

Food–drug interactions: effect of capsaicin on the pharmacokinetics of galantamine in rats

1. Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide, CAP) is a naturally occurring alkaloid extracted from the fruit of Capsicum plant family. It represents an important ingredient in spicy foods consumed throughout the world. However, little is known about the metabolic interactions between CAP and clinically used drugs.

2. This study attempted to investigate the effect of CAP on the pharmacokinetics of galantamine, a competitive and reversible cholinesterase inhibitor. CAP, dexamethasone or sodium salt of carboxymethyl cellulose (CMC-Na) was given to rats for seven consecutive days and on the seventh day galantamine (10 mg/kg) was administered orally. Dexamethasone was used as a CYP inducer and CMC-Na was used as a vehicle.

3. The results showed that the pretreatment of rats with CAP resulted in a decrease in the AUC_0–∞ of galantamine of about 49.70% (p < 0.01) compared with the control group. After oral administration of galantamine (10 mg/kg), the apparent oral clearance of galantamine was raised by 2.05-fold by pretreatment with CAP (p < 0.05). These results demonstrate that the chronic ingestion of high doses of CAP will decrease the bioavailability of galantamine to a significant extent in rats.