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PubMed1989

Pharmacokinetics of scopolamine during caesarean section: relationship between serum concentration and effect.

The pharmacokinetics (radioreceptor assay, RRA) and some of the clinical effects of the anticholinergic agent, scopolamine, were studied in 16 parturients during caesarean section. Following a single 0.005 mg/kg intramuscular injection (deltoid muscle), a very fast rate of absorption was found with mean peak serum concentrations occurring after only 10 min (n = 6). Due to severe bradycardia, 0.5 mg of atropine i.v. had to be given in addition to the i.m. scopolamine treatment to one parturient. The RRA measured the total concentration produced by the two anticholinergic agents in both serum and urine. There was a fundamental difference in the diffusion of scopolamine through the placenta and the blood-lumbar (CSF-barrier (n = 15). There was significant drug penetration in the foeto-placental unit, indicating an efficient drug transfer to the child, but there were measurable levels of the drug in the lumbar CSF in only three cases. The apparent elimination phase half-life of scopolamine in serum was only around 1 h. The urinary excretion of scopolamine and/or its antimuscarinic metabolites lasted only for 6 h (2.63 +/- 1.14% of the dose). The onset of the clinical effects of scopolamine appeared to be delayed, but long-lasting in contrast to the rapid absorption and quick disappearance from the serum. Both the heart rate changes, sedative and antisialogogue effects and serum concentrations did not show any correlation. There appears to be a surprisingly great difference between the pharmacokinetic parameters and the clinical effects of scopolamine.

Absorption↗
PubMed1998

Pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine. A comparison of two injection sites.

BACKGROUND: Intramuscular scopolamine plus morphine premedication is traditionally used when prominent sedative or antisialogogue effect is needed. Knowledge of the pharmacokinetics of scopolamine is limited due to low plasma concentrations found after therapeutic doses. This investigation compares the pharmacokinetics and the clinical responses of this drug combination injected into two commonly used injection sites. METHODS: Twelve ASA class 1 patients scheduled for minor surgery under spinal anaesthesia received scopolamine 6 micrograms/kg plus morphine 200 micrograms/kg injected in either deltoid (group D, n = 6) or gluteal (group G, n = 6) muscle. RESULTS: The peak plasma concentrations of scopolamine after deltoid or gluteal injection (2.2 vs 1.6 micrograms/l) and the time they were reached (17 vs 19 min) were comparable. The absorption of morphine was similar in both groups (Tmax 16 min), but the peak plasma concentrations were higher after deltoid injection (71 vs 49 micrograms/l). The individual variation in the elimination half-lives of both scopolamine and morphine was smaller after deltoid injection (T1/2 scopolamine 1.9 +/- 0.7 vs 2.1 +/- 1.1 h, morphine 1.3 +/- 0.7 vs 2.3 +/- 1.5 h). Moderate slowing (25%) of heart rate was found in both groups. A heavy sedation and antisialogogue effect (VAS) was found in both groups with faster occurrence of maximal effect in group D (60 vs 120-180 min). CONCLUSION: More predictable pharmacokinetics and clinical effects of intramuscular scopolamine plus morphine premedication can be achieved after an injection into deltoid muscle.

Anesthesia, Spinal↗
PubMed2005

Plastic changes and disease-modifying effects of scopolamine in the pilocarpine model of epilepsy in rats.

PURPOSE: We describe the use of a clinically relevant pharmacological intervention that alters the clinical history of status epilepticus (SE)-induced spontaneous recurrent seizures (SRS) in the pilocarpine model and the possible plastic changes underlying such an effect. METHODS: Two hours after pilocarpine-induced SE (320-350 mg/kg, i.p.), rats received scopolamine 1-2 mg/kg i.p. or saline, every 6 h for 3 days. After that, osmotic minipumps were implanted for continuous delivery of scopolamine or saline for an additional 14 days. Animals were video-monitored for 12 h/week during the following 3-month period for the occurrence of SRS and, thereafter, were perfused, processed, and coronal brain sections were stained for acetylcholinesterase (AChE) and for the presence of supragranular mossy fibers (Timm). RESULTS: Treatment with scopolamine led to significantly fewer SRS. Staining for AChE in the dentate gyrus was significantly more intense in naïve animals. The scopolamine group had the least intense AChE staining of all groups. However, regression analysis of the AChE staining for this group did not correlate with the presence or absence of SRS, or the latency or frequency of SRS. Supragranular mossy fiber sprouting developed in all animals experiencing pilocarpine-induced SE, irrespective of whether or not they were treated with scopolamine. CONCLUSIONS: Pilocarpine-induced SE in the presence of scopolamine might produce animals that, despite mossy fiber sprouting, were not seen to exhibit spontaneous seizures. In addition, our data suggest that the encountered changes in the AChE staining in the dentate gyrus that followed treatment with scopolamine do not help to explain its disease-modifying effects.

Acetylcholinesterase↗
PubMed1986

Further studies of the mechanism behind scopolamine-induced reversal of antistereotypic and cataleptogenic effects of neuroleptics in rats.

Scopolamine is known to attenuate the amphetamine antagonistic and cataleptogenic effect of selective DA D-2 antagonists. To study further the influence of other receptor systems three approaches were taken: concomitant treatment with receptor blockers (scopolamine, prazosin and ketanserin) and a selective D-2 antagonist YM 09151-2, testing of a neuroleptic droperidol, with mixed D-2, alpha 1 and 5-HT2 antagonistic properties and testing a selective D-1 antagonist SCH 23390. Scopolamine markedly attenuated both effects of YM 09151-2 and droperidol. In contrast neither prazosin nor ketanserin influenced the effects of YM 09151-2. Furthermore, prazosin did not influence the interaction between scopolamine and YM 09151-2 in the tests of stereotypy and catalepsy. Scopolamine did not change the amphetamine antagonistic potency of SCH 23390, but decreased moderately its cataleptogenic potency. It is concluded that 5-HT2 and alpha 1-adrenergic receptor blockade are of minor importance in order to determine the sensitivity of a DA D-2 antagonist to the reversal induced by scopolamine. Thus, our earlier hypothesis, that DA D-1 receptor blockade is the main mechanism stabilizing these neuroleptic effects against scopolamine reversal, are further supported by the present experiments.

Animals↗
PubMed1995

Comparison of behavioural effects of repeated treatment with methamphetamine plus scopolamine and methamphetamine alone on behavioural sensitization and conditioned response.

We investigated how repeated treatments with methamphetamine (4.0 mg kg-1, i.p.) plus scopolamine (0.5 mg kg-1, i.p.) and methamphetamine alone effected behavioural sensitization and conditioned response in rats. Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of focused stereotyped behaviour than repeated methamphetamine treatment. Stereotyped behaviour induced by methamphetamine plus scopolamine was reproduced by challenge injections of methamphetamine plus scopolamine, methamphetamine, and to a lesser extent by scopolamine challenges. The methamphetamine plus scopolamine-sensitized rats were conditioned to a low frequency tone (300 Hz, 100 dB) associated with the drug state. They exhibited a conditioned response to pairings of the tone (conditioned stimulus) and placebo injections. However, they did not respond to the tone alone or the placebo injections alone. The methamphetamine-sensitized rats failed to demonstrate any conditioning; only the repeated methamphetamine plus scopolamine treatment induced sensitization to the drug-associated tone. Pairings of exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for conditioning to the tone associated with the drug state. We conclude that behavioural sensitization may operate via a reciprocal balance between the dopaminergic and cholinergic inhibitory systems, in favour of a dopaminergic dominance. Conditioning to the drug-associated tone may be mediated via a reciprocal balance between the two transmitter systems.

Animals↗
PubMed1998

Scopolamine-induced impairment of delayed recognition of abstract visual shapes.

Since the limbic system, whose involvement in cognitive processes is well documented, constitutes a major central cholinergic area, the effect of cholinergic drugs on cognitive tasks has been studied extensively. In the present study, we used a long-term visual recognition task to evaluate the persistence of the scopolamine-induced anterograde amnesia beyond drug clearance intervals. Following memorization of a list of abstract shapes, subjects were evaluated on recognition performance immediately after encoding, and after a 3-day interval. Administration of scopolamine (0.4-0.8 mg) 70 min prior to encoding induced a significant (8-16%) deficit in delayed recognition performance. In contrast, a scopolamine challenge on delayed recognition following a drug-free encoding did not influence memory performance. In contrast, even at peak levels, scopolamine did not alter immediate recognition, detection or visual discriminative performances. Hence, the presence of scopolamine during the encoding of the shapes induced a significant long-term memory deficit that persisted after scopolamine clearance. Therefore, this paradigm is useful for imaging regional brain activation during impaired recognition without the confounding direct effects of scopolamine on cerebral blood flow or metabolism, two physiological variables underlying the indirect measurement of brain activation.

Adult↗
PubMed1995

Do increases in markers of vagal activity imply protection from sudden death? The case of scopolamine.

BACKGROUND: Low-dose scopolamine increases heart rate variability (HRV) in patients with a prior myocardial infarction (MI). This observation, combined with the evidence that elevated cardiac vagal activity during acute myocardial ischemia is antifibrillatory, has generated the hypothesis that scopolamine might be protective after MI. We tested low-dose scopolamine in a clinically relevant experimental preparation for sudden death in which other vagomimetic interventions are effective. METHODS AND RESULTS: Nineteen mongrel dogs that survived an anterior MI were used in the study. Occurrence or lack of ventricular fibrillation (VF) due to acute myocardial ischemia during submaximal exercise identified dogs at high and low risk for sudden death. Dose-response curves performed in 12 dogs at high (n = 6) and low (n = 6) risk showed that scopolamine at 3 micrograms/kg exerts the greatest effect on HRV. A second group of 7 high-risk dogs were exposed to an exercise-and-ischemia test after treatment with scopolamine (3 micrograms/kg i.v.). Scopolamine increased the standard deviation of RR intervals by 41%, increased the high-frequency band of spectral analysis by 48%, and decreased resting heart rate by 14%. Despite the increase in markers of vagal activity, VF recurred during the exercise-and-ischemia test in 6 dogs (86%). CONCLUSIONS: The significant increase in HRV induced by acute scopolamine did not result in a decreased risk for VF due to acute myocardial ischemia in association with sympathetic activation. Caution must be applied when extrapolating the potential antifibrillatory activity of an intervention from its influence on autonomic markers.

Animals↗
PubMed1999

Protective effects of pseudoginsenoside-F11 on scopolamine-induced memory impairment in mice and rats.

This study assessed the effects of pseudoginsenoside-F11, a component of Panax quinquefolium L., on scopolamine-impaired memory performance in mice and rats. In the one-trial step-down and step-through passive avoidance tests, although pseudo-ginsenoside-F11 used alone did not affect passive avoidance behaviour in naive mice, the latency of avoidance shortened by intraperitoneal scopolamine (2 mg kg(-1)) was prolonged after intragastric administration of pseudoginsenoside-F11 (2 or 4 mg kg(-1), for five days) in both test systems in mice. In the water-maze test, in mice, the time taken to locate the platform after administration of pseudoginsenoside-F11 was shorter than that after administration of scopolamine (1 mg kg(-1), i.p.). In the two-way active avoidance response test, the latency of avoidance was significantly shorter for the pseudoginsenoside-F11-(1.2 or 2.4 mg kg(-1), i.g. for five days) and scopolamine-treated group than for the group of rats given scopolamine only (2 mg kg(-1), i.p.). The percentage avoidance was also reduced after intraperitoneal injection of scopolamine, but was reversed by administration of pseudo-ginsenoside-F11. These results suggest that pseudoginsenoside-F11 antagonized the memory dysfunction induced by scopolamine. However, the mechanism of the memory facilitative action of pseudoginsenoside-F11 merits further elucidation.

Animals↗
PubMed2005

Effect of a nutritive-tonic drink on scopolamine-induced memory impairment in mice.

The effects of a liquid nutritive and tonic drug (NTD) selected from a modification of the "Kai-xin-shou-yu-shen-qi-wan" prescription, on scopolamine-induced amnesia in mice were investigated using the passive avoidance and water-maze tasks. A popular NTD in Japan that contains 17 crude (natural) drug extracts together with synthetic drugs such as taurine, caffeine, various vitamins and ethanol, and the natural drug extracts is based on a prescription of "Kampo" origin in Chinese medicine. Scopolamine (0.4 mg/kg, i.p.) reduces the step-through latency of the passive avoidance test and fear reaction behavior at 24 and 48 h after treatment. A single oral administration of the NTD (10 ml/kg) increased the step-through latency and the fear reaction behavior score in scopolamine-treated mice. Administration of the natural drug extracts found in the NTD tended to extend the step-through latency in the retention test at 48 h, but not 24 h after the initial scopolamine trial. However, administration of the synthetic drugs found in the NTD did not improve either the step-through latency or the behavioral score. The NTD and the natural drug extracts also improved the scopolamine-induced spatial memory impairment as assessed using the Morris water-maze test. In contrast, the synthetic drugs did not affect the escape latencies. Both NTD and the synthetic drugs increased the locomotor activity in scopolamine-treated mice, whereas the natural drug extracts did not. These results suggest that NTD improves scopolamine-induced amnesia, and that this action is attributable to the natural drug extracts in the NTD.

Animals↗
PubMed1983

Effect of 4-(o-benzylphenoxy)-N-methylbutylamine hydrochloride (MCI-2016) on the scopolamine-induced deficit of spontaneous alternation behavior in rats.

To predict the possible activity on memory disorders, the effect of MCI-2016 was compared with those of physostigmine, choline chloride, methamphetamine, apomorphine, imipramine and calcium hopantenate by applying scopolamine-induced deficit of spontaneous alternation behavior (scopolamine-SA) as a proposed animal model for senile dementia. MCI-2016 was shown to improve the scopolamine-SA at doses of 25 to 100 mg/kg p.o. without producing any remarkable behavioral abnormalities. As for the effect of reference drugs, two types of cholinomimetic drugs (physostigmine and choline chloride) and methamphetamine were shown to be active. In the cases of physostigmine and methamphetamine, however, behavioral abnormalities were observed at those dose levels effective on scopolamine-SA. MIC-2016 potentiated the effect of physostigmine on scopolamine SA at non active doses of 10 to 20 mg/kg p.o. In comparison with the deleterious effect of scopolamine on spontaneous alternation (SA) behavior itself, none of the test drugs except for imipramine were shown to disrupt the SA. Considering the disruptive or improving actions of various agents on SA or scopolamine-SA, it may be suggested that the present model is relatively sensitive to those drugs which affect the cholinergic mechanism either directly or indirectly. Mechanisms of the actions of MCI-2016 and methamphetamine were also discussed with reference to possible involvement of cholinergic mechanisms.

Animals↗
PubMed1993

Involvement of beta-adrenergic systems in the antagonizing effect of paeoniflorin on the scopolamine-induced deficit in radial maze performance in rats.

Paeoniflorin, a major constituent of peony root, has been demonstrated to attenuate the radial maze performance deficit produced by scopolamine. In the present study, to investigate the possible involvement of beta-adrenergic systems in the paeoniflorin antagonism of the scopolamine deficit, the effects of two beta-adrenoceptor antagonists, propranolol and atenolol, on the paeoniflorin effect were examined in male Wistar rats. Paeoniflorin (1 mg/kg, p.o.) significantly attenuated the scopolamine HBr (0.3 mg/kg, i.p.)-induced deficit in the choice accuracy in radial maze performance without changing the running time prolonged by scopolamine. Neither D,L-propranolol HCl, a lipophilic beta-antagonist, at 3 mg/kg, i.p. nor atenolol, a hydrophilic beta 1-antagonist that is known to hardly ever cross the blood-brain barrier, at 1 mg/kg, i.p. impaired maze performance by itself or aggravated the scopolamine-induced deficit in radial maze performance. Both antagonists, however, completely blocked the antagonizing effect of paeoniflorin on the scopolamine deficit. These data suggest that the beta-adrenergic systems, especially peripheral beta 1-adrenergic systems, are involved in the antagonizing effect of paeoniflorin on the scopolamine deficit in radial maze performance in rats.

Animals↗
PubMed2000

The scopolamine-induced impairment of spatial cognition parallels the acetylcholine release in the ventral hippocampus in rats.

We investigated the relationship between the induction of spatial cognition impairment in the 8-arm radial maze task and regional changes (ventral hippocampus (VH), dorsal hippocampus, frontal cortex, and basolateral amygdala nucleus) in brain acetylcholine (ACh) release using microdialysis in rats treated with muscarinic (M) receptor antagonists. In a behavioral study, two M1 antagonists, scopolamine (0.5 mg/kg, i.p. and 20 microg, i.c.v.) and pirenzepine (80 microg, i.c.v.), but not an M2 antagonist, AF-DX116 (40-80 microg, i.c.v.), disrupted spatial cognition in the 8-arm radial maze task. In brain microdialysis with Ringer's solution containing 0.1 mM eserine sulfate, scopolamine and AF-DX116, but not pirenzepine, increased ACh release in the VH. Moreover, in the bilateral injection of scopolamine (2 microg/side), the VH and dorsomedial thalamus nucleus were important regions for scopolamine-induced impairment of spatial cognition. A simultaneous determination of the behavioral changes revealed that scopolamine (0.5 mg/kg, i.p.) markedly decreased the ACh contents and also increased the ACh release in all regions tested. Especially, the changes in the ACh release of the VH closely paralleled the induction of the scopolamine-induced impairment of spatial cognition. These results suggest that the blocking balance between M1 and M2 muscarinic receptor in the VH therefore plays a major role in the spatial cognition impairment induced by scopolamine in the 8-arm radial maze task.

Acetylcholine↗
PubMed1991

Transderm scopolamine for the control of perioperative nausea.

A randomized prospective study of 201 patients in two institutions was performed to evaluate the efficacy of a transderm scopolamine patch in the control of postoperative nausea. Of 201 patients, 180 successfully completed the protocol. Demographically, the groups were similar in age, sex, and surgical procedures. Adverse effects were noted in both treatment and control groups. Forty-seven per cent of the placebo and 49 per cent of the transderm scopolamine group did not experience postoperative side effects. The most common adverse reactions were urinary retention, dry mouth, agitation, nausea, and vomiting. There was a reduction in the number of vomiting episodes in the transderm scopolamine treatment group from the control group (21% transderm scopolamine vs. 36% placebo). These differences became more significant among the subgroups in surgery, especially after orthopedic procedures. Thirty-five per cent of the transderm scopolamine group experienced nausea compared with 65 per cent from the placebo, 11 per cent of the transderm scopolamine experienced vomiting compared to 26 per cent. Transderm scopolamine was effective in reducing but not eliminating postoperative nausea.

Administration, Cutaneous↗
PubMed1989

Transdermal scopolamine: a review of its effects upon motion sickness, psychological performance, and physiological functioning.

Scopolamine is the most effective single drug for the prophylaxis and treatment of motion sickness. However, oral or injected scopolamine displays a comparatively short duration of action (5-6 hours), and leads to deleterious side effects on autonomic and central nervous system cholinergic functions. The transdermal scopolamine system was designed to reduce these problems, but while it does deliver scopolamine over a prolonged time period (72 h), deleterious side effects are also produced. Transdermal scopolamine provides significant motion sickness protection, similar in extent to that provided by oral scopolamine or dimenhydrinate. Its autonomic nervous system effects comprise reduced salivation, bradycardia, and blurred vision due to reduced visual accommodation. The visual problems increase following repeated patch applications, with hypermetropic ("long sighted") individuals particularly at risk. Central nervous system effects comprise reduced memory for new information, impaired attention, and lowered feelings of alertness. Variation in response to transdermal scopolamine has also been reported, both between individuals, and between different patch applications on the same individual.

Accommodation, Ocular↗
PubMed1988

Development and application of a radioreceptor assay for scopolamine.

6 beta,7 beta-Epoxy-3a(1aH,5aH)-tropanyl-(S)-tropate (scopolamine) has proved to be a very effective drug in the prevention of motion sickness, however, the drug has a small therapeutic window, a low bioavailability and a short half-life. A transdermal drug delivery system (Scopoderm TTS) was developed to circumvent these problems as well as the variability in gastric absorption. In order to study the pharmacokinetics of the drug and its glucuronide, a highly sensitive radioreceptor assay with an absolute detection limit of 15 pg scopolamine was developed. In children undergoing minor surgery, a Scopoderm TTS patch of different sizes (according to the age of the children) was applied to the retro-auricular skin. Urine samples were collected and assayed for free and conjugated scopolamine. Furthermore possible anticholinergic effects on the pupil reaction, salivation, blood pressure and heart rate were monitored. The urine excretion of free and glucuronidated scopolamine showed large intra- and interindividual variations. However, in all age groups relatively high percentages of free scopolamine were found, namely 47.5% (3-6 years), 48.3% (7-12 years) and 36.0% (13-18 years) of the sum of free plus glucuronidated scopolamine. During the application of the patch, a prolonged plateau of scopolamine excretion could be found. Although in general the patches were well tolerated, both locally and systematically, moderate anticholinergic effects were observed in patients.

Adolescent↗
PubMedDate not supplied

[Effect of scopolamine on formation and fixation of temporary connections in rats with altered brain serotonin levels].

The influence of scopolamine on elaboration and maintenance of conditioned reflexes of two-way avoidance was studied in rats under conditions of excess and deficit of serotonin in the brain. Administration of scopolamine to intact rats accelerated conditioning and did not prevent fixation of the reflex. Administration of scopolamine to animals with a lowered level of serotonin in the brain (by means of para-chlorophenylalanine) impaired conditioning and induced amnesia. In animals with ablated raphe nuclei, the same dose of scopolamine did not prevent elaboration and maintenance of conditioned reflexes. Accumulation of scopolamine in the brain by means of 5-oxytryptophan abolished acceleration of conditioning, which is specific for scopolamine, and affected the preservation of the reflexes. Against the background of the action of iprozid, scopolamine impaired the conditioning and tended to deteriorate the maintenance of conditioned reflexes. It is assumed that the serotoninergic system exerts a modulating influence on the activity of the brain cholinergic and cholinoreactive mechanisms.

5-Hydroxytryptophan↗
PubMed1981

Scopolamine alone or combined with ephedrine in seasickness: a double-blind, placebo-controlled study.

In seasickness, the central cholinergic-noradrenergic balance is disturbed. Capsules of identical appearance--containing scopolamine hydrobromide 0.3 mg, scopolamine hydrobromide 0.3 mg + ephedrine hydrochloride 25 mg, or placebo--were given prophylactically three times daily to 30 naval cadets during a crossing. In this randomized, double-blind trial the superiority of scopolamine and scopolamine + ephedrine over placebo was confirmed. Ephedrine did not clearly increase the effectiveness of scopolamine. One subject in the scopolamine group and one in the placebo group interrupted the treatment. The symptoms of seasickness as well as the number of side-effects of the drugs decreased on the third day of the study. Scopolamine alone or in combination with ephedrine proved useful in the prevention of seasickness in young healthy male volunteers.

Adult↗
PubMed1998

Effects of U-50,488H on scopolamine-, mecamylamine- and dizocilpine-induced learning and memory impairment in rats.

The role of kappa opioid receptor agonists in learning and memory is controversial. In the present study, the effects of U-50,488H on scopolamine-, mecamylamine- and dizocilpine-induced learning and memory impairments in rats were investigated. Scopolamine (3.3 mumol/kg s.c.), a muscarinic cholinergic antagonist, and mecamylamine (40 mumol/kg s.c.), a nicotinic cholinergic antagonist, significantly impaired learning and memory in rats in a step-through type passive avoidance test. Administration of U-50,488H (0.17 or 0.51 mumol/kg s.c.) 25 min before the acquisition trial reversed the impairment of learning and memory induced by scopolamine and mecamylamine. Although low doses of scopolamine (0.17 mumol/kg) and mecamylamine (12 mumol/kg) had no effect, concurrent administration of both antagonists induced impairment of learning and memory. Scopolamine significantly increased acetylcholine release in the hippocampus as determined by in vivo brain microdialysis. On the other hand, mecamylamine significantly decreased acetylcholine release. U-50,488H completely blocked the decrease in acetylcholine release induced by mecamylamine, whereas it only partially blocked the increase of acetylcholine induced by scopolamine. On the other hand, an endogenous kappa opioid receptor agonist, dynorphin A (1-13), did not block the increase in acetylcholine release induced by scopolamine. The antagonistic effect of U-50,488H was abolished by pretreatment with nor-binaltorphimine (4.9 nmol/rat i.c.v.), a selective kappa opioid receptor antagonist. U-50,488H did not affect the impairment of learning and memory induced by the blockade of NMDA receptors by dizocilpine ((+)-MK-801). These results suggest that U-50,488H reverses the impairment of learning and memory induced by the blockade of cholinergic transmission and abolishes the decrease of acetylcholine release induced by mecamylamine via the kappa receptor-mediated opioid neuronal system.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗