Ultrasonography for Eating and Swallowing Assessment: A Narrative Review of Integrated Insights for Noninvasive Clinical Practice.

Dysphagia is a syndrome of abnormal eating function resulting from a variety of causative diseases, and is associated with malnutrition. To date, the swallowing function has been difficult to examine without the use of invasive and expensive methods, such as the videofluorographic swallowing study or fiberoptic endoscopic evaluation of swallowing. In recent years, progress has been made in the clinical application of ultrasound equipment for the evaluation of body compositions near the body surface, including the assessment of nutritional status. Ultrasound examination is a noninvasive procedure and relatively inexpensive, and the equipment required is highly portable thanks to innovations such as wireless probes and tablet monitoring devices. The process of using ultrasound to visualize the geniohyoid muscle, digastric muscle, mylohyoid muscle, hyoid bone, tongue, masseter muscle, genioglossus muscle, orbicularis oris muscle, temporalis muscle, pharynx, esophagus, and larynx, and the methods used for evaluating these structures, are provided in this study in detail. This study also aims to propose a protocol for the assessment of swallowing-related muscles that can be applied in real-world clinical practice for the diagnosis of sarcopenic dysphagia, which can occur in elderly patients with sarcopenia, and has received much attention in recent years.

Gait improvement in stroke patients by Gait Exercise Assist Robot training is related to trunk verticality.

[Purpose] Various types of Gait Exercise Assist Robot (GEAR) have been developed recently, some of which have enabled early improvement in patients with stroke. However, none has yet resulted in independent walking in these patients. Hence, we conducted an exploratory study of the effect of GEAR on achieving independent walking in stroke patients. [Participants and Methods] The participants were 16 patients with severe stroke. We evaluated patients' ability to walk independently after GEAR training. The outcome measure was Stroke Impairment Assessment Set (SIAS) motor score (Hip Flexion, Knee Extension, Foot Pat, Abdominal and Verticality). Differences in five SIAS motor scores were compared between the independent and non-independent walking groups. [Results] There was statistically significant difference between the groups in terms of Verticality among the 5 SIAS items used in the present research . Verticality of SIAS score of 1 was the cut-off value for distinguishing walking independence. [Conclusion] Verticality of SIAS may be a marker of potential walking independence that can be used in rehabilitation plans using walking-assist robots in patients with stroke.

Benefits of a Balance Exercise Assist Robot in the Cardiac Rehabilitation of Older Adults with Cardiovascular Disease: A Preliminary Study.

We examined whether adding robot-supported balance exercises to cardiac rehabilitation improves the ability to balance in older adults with cardiovascular disease (CVD). We conducted a prospective study in 52 older adults who had been hospitalized for worsening CVD. Once weekly for four months, for a total of sixteen sessions as outpatients, the subjects used a Balance Exercise Assist Robot (BEAR) to perform balance exercises and an ergometer for aerobic exercises. Participants' mean age was 76.9 ± 6.8 years (range, 65−95 years), and their mean brain natriuretic protein level was 164.0 ± 190.0 pg/mL. After the intervention, participants showed significant improvements in gait speed (before, 1.06 ± 0.33 m/s; after, 1.23 ± 0.30 m/s; p < 0.001), Short Physical Performance Battery score (before, 10.02 ± 2.25; after, 10.88 ± 1.79; p ˂ 0.001), timed up-and-go (before, 11.11 ± 5.07 s; after, 9.45 ± 3.45 s; p ˂ 0.001), and knee extension (before, 26.97 ± 11.78 kgf; after, 30.13 ± 13.04 kgf; p = 0.001). Cardiac rehabilitation including exercises using BEAR improved physical functioning and the ability to balance in older adults with CVD. Frail and prefrail patients improved, whereas robust ones did not change.

Possibility of Using Quantitative Assessment with the Cube Copying Test for Evaluation of Visuo-spatial Function in Patients with Alzheimer's Disease.

OBJECTIVES: The aim of this study was to investigate the clinical usefulness of the Cube Copying Test (CCT) for quantitative assessment of visuo-spatial function in patients with Alzheimer's disease (AD). METHODS: The CCT, Raven's Colored Progressive Matrices (RCPM), and other neuropsychological tests were administered to 152 AD outpatients. For the quantitative assessment of CCT, we scored the points of connection (POC) and the number of plane-drawing errors (PDE) and categorized the pattern classification (PAC). We also measured Functional Assessment Staging (FAST) to assess the severity of AD. The relationships among CCT, RCPM, and FAST were then analyzed. RESULTS: The mean POC and PDE scores were 2.7 and 3.6, respectively, and the median PAC score was 6.0. PDE and PAC showed a linear relationship, but POC and PDE, and POC and PAC did not. Each component of CCT showed a significant correlation with RCPM scores. PDE and PAC had closer correlations with RCPM scores than POC did. The PDE and PAC results were significantly different among most of the FAST stages. CONCLUSIONS: Quantitative assessment using CCT may be effective for the quick determination of the visuo-spatial function in AD patients.

Usefulness of Electromyography to Predict Future Muscle Weakness in Clinically Unaffected Muscles of Polio Survivors.

BACKGROUND: Post-polio syndrome-induced muscle weakness may develop in limbs that have had normal muscle strength and have been considered unaffected by polio. OBJECTIVE: To investigate the utility of electromyography (EMG) for predicting future muscle weakness in clinically unaffected limb muscles of polio survivors. DESIGN: Retrospective study. SETTING: Academic polio clinic. PARTICIPANTS: Polio survivors (N = 77) who underwent EMG between April 2008 and March 2010 and were followed for at least 2 years. MATERIALS AND METHODS: Chart reviews were conducted to extract baseline EMG and manual muscle strength test (MMT) results to investigate the relationship between baseline EMG abnormalities and change in muscle strength over 2 years for various upper and lower limb muscles that control movement in the limb joints. MAIN OUTCOME MEASUREMENTS: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EMG findings for prediction of subsequent muscle weakness. RESULTS: EMG data were available for 44 deltoid, 59 biceps brachii, 60 triceps brachii, 59 vastus lateralis, 59 tibialis anterior, and 55 gastrocnemius (medial head) muscles. The percentage of muscles with an initial MMT of grade 5 that developed weakness over 2 years of follow-up was approximately 15% for most muscle types. Sensitivity of EMG to predict subsequent weakness was higher in the lower limbs (0.67-1.00). Specificity was higher in the biceps brachii (0.83). PPV was higher in the biceps brachii (0.50). NPV was higher in the lower limbs (0.89-1.00) but lower in the deltoid (0.75). CONCLUSION: EMG abnormalities were detected in some clinically normal muscles of polio survivors. EMG abnormalities predicted muscle weakness 2 years later, although the strength of this relationship varied depending on the muscle.

Model for prompt and effective classification of motion recovery after stroke considering muscle strength and coordination factors.

BACKGROUND: Muscle synergies are now widely discussed as a method for evaluating the existence of redundant neural networks that can be activated to enhance stroke rehabilitation. However, this approach was initially conceived to study muscle coordination during learned motions in healthy individuals. After brain damage, there are several neural adaptations that contribute to the recovery of motor strength, with muscle coordination being one of them. In this study, a model is proposed that assesses motion based on surface electromyography (sEMG) according to two main factors closely related to the neural adaptations underlying motor recovery: (1) the correct coordination of the muscles involved in a particular motion and (2) the ability to tune the effective strength of each muscle through muscle fiber contractions. These two factors are hypothesized to be affected differently by brain damage. Therefore, their independent evaluation will play an important role in understanding the origin of stroke-related motor impairments. RESULTS: The model proposed was validated by analyzing sEMG data from 18 stroke patients with different paralysis levels and 30 healthy subjects. While the factors necessary to describe motion were stable across heathy subjects, there was an increasing disassociation for stroke patients with severe motor impairment. CONCLUSIONS: The clear dissociation between the coordination of muscles and the tuning of their strength demonstrates the importance of evaluating these factors in order to choose appropriate rehabilitation therapies. The model described in this research provides an efficient approach to promptly evaluate these factors through the use of two intuitive indexes.

[Support for Patients and Their Family Using Artificial Intelligence].

For patients with dementia and their family, artificial intelligence (AI) has been utilized to support diagnosis and evaluation. In addition, communication robots equipped with AI offer a way to maintain the cognitive functions of patients with dementia. Moreover, AI is currently used for fall prevention and to define the needs of patients and their family and to convey them to develop new devices. The expectation for AI is to make the quality of life for patients and their family's better than ever.

Motor Control System for Adaptation of Healthy Individuals and Recovery of Poststroke Patients: A Case Study on Muscle Synergies.

Understanding the complex neuromuscular strategies underlying behavioral adaptation in healthy individuals and motor recovery after brain damage is essential for gaining fundamental knowledge on the motor control system. Relying on the concept of muscle synergy, which indicates the number of coordinated muscles needed to accomplish specific movements, we investigated behavioral adaptation in nine healthy participants who were introduced to a familiar environment and unfamiliar environment. We then compared the resulting computed muscle synergies with those observed in 10 moderate-stroke survivors throughout an 11-week motor recovery period. Our results revealed that computed muscle synergy characteristics changed after healthy participants were introduced to the unfamiliar environment, compared with those initially observed in the familiar environment, and exhibited an increased neural response to unpredictable inputs. The altered neural activities dramatically adjusted through behavior training to suit the unfamiliar environment requirements. Interestingly, we observed similar neuromuscular behaviors in patients with moderate stroke during the follow-up period of their motor recovery. This similarity suggests that the underlying neuromuscular strategies for adapting to an unfamiliar environment are comparable to those used for the recovery of motor function after stroke. Both mechanisms can be considered as a recall of neural pathways derived from preexisting muscle synergies, already encoded by the brain's internal model. Our results provide further insight on the fundamental principles of motor control and thus can guide the future development of poststroke therapies.

Training with a balance exercise assist robot is more effective than conventional training for frail older adults.

AIM: To examine the efficacy of postural strategy training using a balance exercise assist robot (BEAR) as compared with conventional balance training for frail older adults. METHODS: The present study was designed as a cross-over trial without a washout term. A total of 27 community-dwelling frail or prefrail elderly residents (7 men, 20 women; age range 65-85 years) were selected from a volunteer sample. Two exercises were prepared for interventions: robotic exercise moving the center of gravity by the balance exercise assist robot system; and conventional balance training combining muscle-strengthening exercise, postural strategy training and applied motion exercise. Each exercise was carried out twice a week for 6 weeks. Participants were allocated randomly to either the robotic exercise first group or the conventional balance exercise first group. MAIN OUTCOME MEASURES: preferred and maximal gait speeds, tandem gait speeds, timed up-and-go test, functional reach test, functional base of support, center of pressure, and muscle strength of the lower extremities were assessed before and after completion of each exercise program. RESULTS: Robotic exercise achieved significant improvements for tandem gait speed (P = 0.012), functional reach test (P = 0.002), timed up-and-go test (P = 0.023) and muscle strength of the lower extremities (P = 0.001-0.030) compared with conventional exercise. CONCLUSIONS: In frail or prefrail older adults, robotic exercise was more effective for improving dynamic balance and lower extremity muscle strength than conventional exercise. These findings suggest that postural strategy training with the balance exercise assist robot is effective to improve the gait instability and muscle weakness often seen in frail older adults. Geriatr Gerontol Int 2017; 17: 1982-1990.

Efficacy of Botulinum Toxin A Treatment for Pes Varus during Gait.

BACKGROUND: The efficacy of botulinum toxin A (BoNTA) injection on spasticity is usually measured using Modified Ashworth Scale (MAS), but this only evaluates muscle tone at rest and has poor reliability. There are no reports that quantitatively evaluate pes varus during walking after botulinum treatment. The purpose of this study was to evaluate the efficacy of BoNTA injection on pes varus during gait using 3-dimensional motion analysis. METHODS: Twenty-four hemiplegic patients with spastic pes varus deformity during gait received BoNTA injection into lower limb muscles. MAS score, comfortable overground gait velocity, and pes varus angle during treadmill walking were evaluated before, 2, 6, and 12 weeks after the injection. Five healthy subjects were also recruited to develop the pes varus/valgus angle as a normal reference. RESULTS: The median MAS scores were significantly lower at 2 and 6 weeks after the injection. The maximum pes varus angle during the swing phase was significantly lower at 2, 6, and 12 weeks after the injection. It was significantly lower at 6 weeks after the injection during stance phase. The comfortable overground gait velocity was also improved after the injection. However, 2 patients experienced pain during gait and their pes varus angle increased during the follow-up period. CONCLUSIONS: BoNTA injection improved pes varus angle during gait. Evaluating motion in addition to spasticity at rest is recommended because improvements in limb function do not always parallel improvements in spasticity at rest.

Sociocultural beliefs, as well as goodness of fit, influence the effectiveness of coping in Japanese workers.

BACKGROUND: Although the goodness-of-fit hypothesis (GOFH) is one of the most important theories in research about the effect of coping on distress related to different stressful situations, there has been a mixed response to it in the literature. PURPOSE: The present study examined whether the effect of the sociocultural context in stressful situations is consistent with the GOFH. The study investigated sociocultural beliefs about the appropriateness of different coping strategies in a given group as the sociocultural context. METHOD: Japanese employees (N = 1,156) of an information technology company reported their appraisal of stressors' controllability, the coping strategies they employed for the stressors, their sociocultural beliefs about coping strategies, and their psychological distress in response to the stressors. RESULTS: The GOFH was supported only for problem-focused coping with task stressors and not for interpersonal stressors. The applicability of the GOFH differed by sociocultural beliefs about coping, namely an appraisal of what coworkers might think about the appropriateness of the coping method. CONCLUSION: These results suggest that it is important for managing stress to consider the sociocultural context as well as the GOFH.

Anxiolytic actions of motilin in the basolateral amygdala.

Motilin is a 22-amino-acid gastrointestinal polypeptide that was first isolated from the porcine intestine. We identified that motilin receptor is highly expressed in GABAergic interneurons in the basolateral nucleus (BLA) of the amygdala, the structure of which is closely involved in assigning stress disorder and anxiety. However, little is known about the role of motilin in BLA neuronal circuits and the molecular mechanisms of stress-related anxiety. Whole-cell recordings from amygdala slices showed that motilin depolarized the interneurons and facilitated GABAergic transmission in the BLA, which is mimicked by the motilin receptor agonist, erythromycin. BLA local injection of erythromycin or motilin can reduce the anxiety-like behavior in mice after acute stress. Therefore, motilin is essential in regulating interneuron excitability and GABAergic transmission in BLA. Moreover, the anxiolytic actions of motilin can partly be explained by modulating the BLA neuronal circuits. The present data demonstrate the importance of motilin in anxiety and the development of motilin receptor non-peptide agonist as a clear target for the potential treatment of anxiety disorders.

Preliminary trial of postural strategy training using a personal transport assistance robot for patients with central nervous system disorder.

OBJECTIVE: To examine the efficacy of postural strategy training using a personal transport assistance robot (PTAR) for patients with central nervous system disorders. DESIGN: Single-group intervention trial. SETTING: Rehabilitation center at a university hospital. PARTICIPANTS: Outpatients (N=8; 5 men, 3 women; mean age, 50±13y) with a gait disturbance (mean time after onset, 34±29mo) as a result of central nervous system disorders were selected from a volunteer sample. INTERVENTIONS: Two methods of balance exercise using a PTAR were devised: exercise against perturbation and exercise moving the center of gravity. The exercises were performed twice a week for 4 weeks. MAIN OUTCOME MEASURES: Preferred and tandem gait speeds, Functional Reach Test, functional base of support, center of pressure (COP), muscle strength of lower extremities, and grip strength were assessed before and after the completion of the exercise program. After the exercise program, enjoyment of exercise was investigated via a visual analog scale questionnaire. RESULTS: After the program, statistically significant improvements were noted for tandem gait speeds (P=.009), Functional Reach Test (P=.003), functional base of support (P=.014), and lower extremity muscle strength (P<.001-.042). On the other hand, preferred gait speeds (P=.151), COP (P=.446-.714), and grip power (P=.584) did not change. Finally, subjects rated that this exercise was more enjoyable than traditional balance exercises. CONCLUSIONS: Dynamic balance and lower extremity muscle strength were significantly improved in response to postural strategy training with the PTAR. These results suggest that postural strategy training with the PTAR may contribute to fall prevention of patients with a balance disorder.

Association between psychological distress and a sense of contribution to society in the workplace.

BACKGROUND: Globally, mental health promotion related to psychological distress in the workplace has become a great concern, and a focus of much research attention. However, a sense of contribution to society and sense of bonding with the workplace have not been examined in relation to psychological distress. Thus, the purpose of this study is to examine whether these two factors are associated with psychological distress. METHODS: We conducted a cross-sectional survey of 1137 full-time employees who worked in systems engineering, sales, or administration at a Japanese company. Participant's sense of contribution to society, sense of bonding with the workplace, psychological distress, and qualitative job stress (quantitative and qualitative workloads, job-control latitude, and support from supervisors, co-workers and family) were assessed with a questionnaire. We performed multiple logistic regression analyses to examine associations between psychological distress and sense of contribution to society and of bonding with the workplace. RESULTS: A high sense of contribution to society was significantly associated with a high sense of bonding with the workplace (Spearman's ρ = 0.47, p < 0.01). A sense of contribution to society was negatively associated with psychological distress after adjusting for job stress factors (OR = 2.05, 95% CI 0.99-4.23) or sociodemographic characteristics of participants (OR = 2.92, 1.53-5.59). After adjusting for job stress factors as well as sociodemographic characteristics, the association became weaker. A sense of bonding with the workplace was negatively associated with psychological distress after adjusting for sociodemographic characteristics (OR = 2.49, 1.29-4.79). However, this association was not observed after adjusting for job stress factors. CONCLUSIONS: Psychological distress in the workplace was associated with sense of contribution to society. Therefore, workplace mental health promotion should consider the workers' sense of contribution to society.

Discovery of novel motilin antagonists: Conversion of tetrapeptide leads to orally available peptidomimetics.

We successfully discovered peptidomimetic motilin antagonists (17c and 17d) through the improvement of physicochemical properties of a tetrapeptide antagonist (2). Furthermore, with oral administration and based on motilin antagonistic activity, both compounds suppressed motilin-induced colonic and gastric motility in conscious dogs.

An orally active motilin receptor antagonist, MA-2029, inhibits motilin-induced gastrointestinal motility, increase in fundic tone, and diarrhea in conscious dogs without affecting gastric emptying.

The pharmacological properties of MA-2029, a selective and competitive motilin receptor antagonist, were investigated in conscious dogs after oral administration. Gastrointestinal contractile activity was recorded by chronically implanted force transducers. The proximal gastric volume was measured with a barostat under constant pressure. Gastric emptying was examined using the paracetamol absorption test. MA-2029 (0.3-10 mg/kg, p.o.) administered in the interdigestive state inhibited gastrointestinal contractions induced by motilin (3 microg/kg, i.v.) in a dose-dependent manner. MA-2029 (0.3-3 mg/kg, p.o.) also inhibited the occurrence of spontaneous phase III contractions, even though MA-2029 had no effect on basal gastrointestinal motility or basal gastric emptying even at 10 and 30 mg/kg p.o. The inhibitory effect of MA-2029 on motilin-induced gastrointestinal motility corresponded to its plasma concentration. Motilin (0.3 microg/kg/h, i.v. infusion) reduced the proximal gastric volume by about 50% of control during isobaric distension. This effect was also inhibited by MA-2029 (1-10 mg/kg, p.o.) in a dose-dependent manner. In the digestive state, injection of motilin (3 microg/kg, i.v.) induced diarrhea in 9 of 11 dogs. MA-2029 (1-30 mg/kg, p.o.) reduced the incidence of diarrhea induced by motilin in a dose-dependent manner. The results indicate that MA-2029 inhibits hypermotility induced by motilin in conscious dogs without having an effect on the basal gastrointestinal tone or gastric emptying rate. MA-2029 may be useful in treating gastrointestinal disorders in which the pathogenesis involves the elevation of circulating motilin.

Relative importance of the area and shape of patches to the diversity of multiple taxa.

Although enhancing reserve shape has been suggested as an alternative to enlarging nature reserves, the importance of reserve shape relative to reserve area remains unclear. Here we examined the relative importance of area and shape of forest patches to species richness, species composition, and species abundance (abundance of each species) for 3 taxa (33 birds, 41 butterflies, and 91 forest-floor plants) in a fragmented landscape in central Hokkaido, northern Japan. We grouped the species according to their potential edge responses (interior-, neutral-, and edge-species groups for birds and forest-floor plants, woodland- and open-land-species groups for butterflies) and analyzed them separately. We used a shape index that was independent of area as an index of shape circularization. Hierarchical partitioning and variation partitioning revealed that patch area was generally more important than patch shape for species richness and species composition of birds and butterflies. For forest-floor plants, effects of patch area and shape were small, whereas effects of local forest structure were large. Patch area and circularization generally increased abundances of interior species of birds and forest-floor plants and woodland species of butterflies. Nevertheless, only patch circularization increased abundances of 1 woodland species of butterfly and 2 and 6 interior species of birds and forest-floor plants, respectively. We did not find any significant interaction effects between patch area and shape. Our results suggest that although reserves generally should be large and circular, there is a trade-off between patch area and shape, which should be taken into consideration when managing reserves.

Effects of mitemcinal (GM-611), an orally active erythromycin-derived prokinetic agent, on delayed gastric emptying and postprandial glucose in a new minipig model of diabetes.

AIMS: This study was conducted to evaluate the suitability of a new minipig model for investigating aspects of diabetes such as delayed gastric emptying and glucose metabolism abnormalities, and to test the effects of mitemcinal (GM-611), an orally active erythromycin-derived motilin receptor agonist, on gastric emptying and postprandial glucose in normal and diabetic minipigs. METHODS AND RESULTS: Intravenous injection of 300 mg/kg streptozotocin (STZ) to 5-week-old minipigs induced moderate hyperglycemia (about 200 mg/dl) for >80 weeks without insulin treatment. Decreased insulin production (P<.05), increased area under the glucose curve (P<.05), and slower glucose disappearance (P<.05) were demonstrated, and there was no severe inhibition of body weight gain, liver failure, or renal failure. Gastric emptying was significantly delayed in diabetic minipigs (P<.05) at 80 weeks, but not at 40 weeks, post-STZ. Oral administration of mitemcinal (5 mg/kg) at 80 weeks accelerated gastric emptying and induced a similar postprandial glucose profile in normal and diabetic minipigs with delayed gastric emptying. CONCLUSIONS: The new diabetic minipig model showed suitability for investigating diabetes, gastric emptying, and plasma glucose excursions. Since delayed gastric emptying and irregular plasma glucose excursions are characteristic of diabetic gastroparesis, the accelerating and regulating effects of mitemcinal on this model add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis.

Mitemcinal (GM-611), an orally active motilin receptor agonist, improves delayed gastric emptying in a canine model of diabetic gastroparesis.

1. The aim of the present study was to evaluate the effects of mitemcinal (GM-611), an orally active motilin receptor agonist, on delayed gastric emptying in a canine model of diabetic gastroparesis and to compare these effects with those of cisapride. 2. Moderate hyperglycaemia was induced by a single intravenous injection of a mixture of streptozotocin (30 mg/kg) and alloxan (50 mg/kg). Dogs that maintained moderate hyperglycaemia (fasting plasma glucose 200-300 mg/dL) without insulin treatment were selected and gastric emptying in these dogs was determined by the paracetamol method. 3. One year after the onset of diabetes, there was no difference in the gastric emptying of normal and diabetic dogs. However, after 5 years, the diabetic dogs showed delayed gastric emptying. The motor nerve conduction velocity of the tibial nerve was significantly lower in diabetic dogs compared with normal dogs at both time points. 4. Histopathological examination at the end of the study showed that there were fewer nerve fibres in both dorsal vagal and tibial nerves of diabetic dogs compared with normal dogs. The onset of delayed gastric emptying is thought to have occurred gradually, in parallel with abnormal autonomic nerve function induced by the long period of moderate hyperglycaemia. 5. Oral administration of mitemcinal (0.125, 0.25 or 0.5 mg/kg) dose-dependently accelerated delayed gastric emptying, significant at 0.5 mg/kg, in diabetic dogs, whereas cisapride (1, 3 or 10 mg/kg) had no significant effect. These results add to the existing evidence that mitemcinal is likely to be useful for treating diabetic gastroparesis.

Oral administration of MA-2029, a novel selective and competitive motilin receptor antagonist, inhibits motilin-induced intestinal contractions and visceral pain in rabbits.

The pharmacological properties of MA-2029, a novel motilin receptor antagonist, were investigated. In vitro, MA-2029 (1 to 30 nM) competitively inhibited motilin-induced contractions in isolated rabbit duodenal longitudinal muscle strips, with a pA2 value of 9.17+/-0.01 (n=5). However, contractile responses to acetylcholine and substance P were unaffected even at 1 microM of MA-2029. MA-2029 concentration-dependently inhibited the binding of [125 I]motilin to motilin receptors in a homogenate of rabbit colon smooth muscle tissue and membranes of HEK 293 cells expressing human motilin receptors. The pKi of MA-2029 was 8.58+/-0.04 in the rabbit colon homogenate (n=4) and 8.39 in the HEK 293 cells (mean of duplicate experiments). In vivo, orally-administered MA-2029 (3 to 30 mg/kg) dose-dependently inhibited colonic contractions induced by motilin (3 microg/kg, i.v.) in conscious rabbits. Inhibition was caused by all doses at 30 min after administration and by 10 mg/kg or more at 4 h after administration. The plasma concentration of MA-2029 correlated with its inhibitory effect. Furthermore, the oral administration of MA-2029 (0.3 to 3 mg/kg) also inhibited abdominal muscle contractions (an index of the visceral pain) induced by intravenous infusion of motilin (3 microg/kg/h) during colorectal distension in conscious rabbits. These results indicate that MA-2029 is an orally active, selective and competitive motilin receptor antagonist. It is suggested that this compound may be useful for gastrointestinal disorders associated with disturbed gastrointestinal motility such as irritable bowel syndrome.