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The cannabinoid system has been suspected to play a role in the mechanisms of action of dipyrone and paracetamol. Our purpose was to measure the local endocannabinoid and N-acylethanolamide levels in the brain and spinal cord of rats following dipyrone and paracetamol administration. Nociception was assessed 1, 5, and 12 h following drug injections in Wistar rats, using tail-flick and hot-plate tests. The antinociceptive effects of dipyrone (150, 300, and 600 mg/kg, i.p.) and paracetamol (30, 100, and 300 mg/kg, i.p.) were observed. After administration of the highest doses of dipyrone and paracetamol, endocannabinoid (N-arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG)) and N-acylethanolamide (palmitoylethanolamide (PEA), oleoylethanolamide (OEA)) levels were measured in the periaqueductal gray (PAG), rostral ventromedial medulla (RVM), and spinal cords of rats using tandem mass spectrometry with liquid chromatography. Increased 2-AG levels were observed in the PAG and the RVM 12 h after paracetamol injection; dipyrone exerted no action on 2-AG levels. Analgesic administrations led to a reduction in AEA levels in the RVM and spinal cord; similar decreases in PEA and OEA levels were observed in the RVM and the spinal cord. Dipyrone and paracetamol administrations appear to exert complicated effects on endocannabinoid and N-acylethanolamide levels in rats.

Purpose: Paracetamol has been shown to exert anxiolytic-like effects mediated by endocannabinoids via cannabinoid CB1 receptors. Dipyrone is an analgesic with similar effects to paracetamol rather than non-steroidal anti-inflammatory drugs. Involvement of central structures to its effects are long under debate, whereas recent findings suggesting contribution of cannabinoid CB1 receptors to its antinociceptive effect support this argument. Taken together, the purpose of this study was to investigate whether dipyrone possesses anxiolytic-like behavior; contribution of cannabinoid CB1 and CB2 receptors and TRPV1 receptors will be determined in case of observing any effect of dipyrone in anxiety tests. Material and Methods: Balb-c mice effects of dipyrone (150, 300, 600 mg/kg, i.p.) were assessed in three-chamber social interaction, open-field, elevated plus-maze and rota rod tests. The cannabinoid CB1 antagonist AM251 (1 mg/kg i.p.), the CB2 antagonist SR 144528 (1 mg/kg i.p.) and the TRPV1 antagonist capsazepine (3 mg/kg i.p.) were going to be administered before dipyrone injections if any effect of dipyrone occurs. Results: Dipyrone had no effect at any dose in behavioral tests (three-chamber social interaction, open-field, elevated plus-maze and rota rod tests). Therefore, dipyrone is not tested together with the cannabinoid CB1 and CB2 antagonists and the TRPV1 receptor antagonist. Conclusion: Unlike paracetamol, dipyrone did not possess anxiolytic-like effects in mice. Discrepancies in experimental models and methodologies may be the reason of our results.

Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as “non-opioid analgesics” and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.

Vibration analysis of rods that are subjected to rotation is presented. It is shown that flexural-flexural, longitudinal-flexural and torsional-flexural wave coupling occur due to the Coriolis Effect. First, we carried out our analysis for thin rods where the wavelength is much larger than the radius. It is shown that the wavenumbers change due to the Coriolis Effect. Then, we characterize the 3-D wave propagation in rotating rods by using the Finite Element Method (FEM) in order to determine the corresponding wavenumber shifts for each type of wave. We show that for different drive frequency (omega(0)) and rotation rate (Omega), wave couplings exhibit different characteristics. For flexural-flexural wave coupling, the wavenumber increases for the primary flexural wave whereas the wave number decreases for the coupled flexural wave where Omega < omega(0). For the Coriolis coupling between flexural-longitudinal waves, the wavenumber increases for the flexural wave and decreases for the longitudinal wave where Omega < omega(0). For the Coriolis coupling between flexural-torsional waves, the wavenumber increases for both flexural and torsional waves. (C) 2020 Elsevier Ltd. All rights reserved.

Although dipyrone is a widely used analgesic and antipyretic, its mechanism of action is not fully clarified. Recent studies have drawn attention to its central effects and its relationship with the endocannabinoid system. The endocannabinoid system plays important roles in processes such as anxiety, depression, fear, and learning-memory. In this study, we aimed to investigate whether endocannabinoid levels change in the amygdala in chronic unpredictable mild stress model in mice and whether cannabinoid and TRPV1 receptors mediate antidepressant and anxiolytic effects of dipyrone. Mice were submitted to chronic unpredictable mild stress protocol of 6-weeks, then behavioral test were performed. In the first part of the study, dipyrone was injected at doses of 150, 300, and 600 mg/kg (i.p.) during behavioral tests. In the second part, the CB1 antagonist AM 251 (1 mg/kg, i.p.), the CB2 antagonist AM630 (1 mg/kg, i.p.), and the TRPV1 antagonist capsazepine (3 mg/kg, i.p.) were administered alone or in combination with 300 mg/kg dipyrone to observe if these receptors mediate dipyrone effects. Endocannabinoid and N-acylethanolamines levels were measured by LC-MS/MS in amygdala. Our results showed that there were no changes in AEA, 2-AG, PEA, OAE levels in the amygdala in mice exposed to chronic unpredictable mild stress model; dipyrone exerted antidepressant and anxiolytic effects at doses of 300 and 600 mg/kg; its anxiolytic effect appears to be mediated via CB1 receptors, whereas TRPV1 receptors seems to mediate its antidepressant action.

Objective: The effects of antipsychotic drugs, of whose different classes can be used in the treatment of patients with resistant to schizophrenia, on the fetus and the benefits of the treatment to the mother should be taken into consideration before making a decision about initiating treatment. This study aimed to examine the effects of prenatal exposure to various antipsychotic agents on learning and memory in adult rats.Method: In this study, antipsychotic drugs from different chemical classes (2 mg/kg haloperidol, 100 mg/kg thioridazine, 200 mg/kg sulpiride, 20 mg/kg chlorprothixene, 40 mg/kg clozapine, 10 mg/kg fluphenazine, 20 mg/kg chlorpromazine) and water for the control group were administered to pregnant Sprague-Dawley dams through gavage during the pregnancy period. In total, 16 groups were created and tested in the Morris water maze by dividing offspring of eight mother rats into male and female rat groups (n=10) on postpartum day 60. Learning was tested with hidden platform task and ...

BackgroundFor centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.ObjectiveThe goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2.Material and methodsScratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2.ConclusionOur findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

Background Combining drugs not only reduces specific adverse effects of each of the drug at a higher dose but also may lead to enhanced efficacy. Tapentadol is a recently discovered analgesic possessing μ-opioid receptor agonism and noradrenaline re-uptake inhibition in a single molecule. Taking into consideration, the pharmacological similarities between opioids and cannabinoids, we assumed that combination of cannabinoids with noradrenaline re-uptake inhibitors might also be effective. We therefore aimed to determine whether combining 1:1, 1:3 and 3:1 fixed ratios of the synthetic cannabinoid WIN 55,212-2 and the selective noradrenaline re-uptake inhibitor maprotiline exert anti-allodynic synergy on nerve-injured neuropathic mice. Methods Partial tight ligation of the sciatic nerve was made in mice; on pre-operative and post-operative 15 days basal mechanical allodynia, cold allodynia and motor function were assessed using von Frey filaments, hot/cold plate and rota rod apparatus. Results Mechanical and cold allodynia developed in all groups on post-operative 15 days. Development of cold allodynia was statistically significant in all groups (p

Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch. Як вважають, глутамат є основним збуджуючим нейротрансмітером у нейронних мережах, відповідальних за поведінкові моторні прояви при почутті свербіжу. β-лактамні антибіотики мають нейропротективні властивості, оскільки забезпечують посилену експресію глутаматного транспортера GLT-1. Ми з’ясовували, чи здатне повторне введення β-лактамного антибіотика цефтриаксону пригнічувати викликані ін’єкціями серотоніну поведінкові моторні прояви (чухальні рухи), пов’язані з індукцією почуття свербіжу (подібно до впливу цього агента на біль) у мишей. Хронічні (але не поодинокі) введення цефтриаксону викликали зменшення кількості рухів чухання. Селективний блокатор транспортера GLT-1 дигідрокаїнова кислота частково, але істотно перешкоджала цьому ефекту цефтриаксону. Наші спостереження дають підстави вважати, що активація GLT-1 β-лактамними антибіотиками є перспективним підходом у лікуванні хронічного свербіжу.

Objective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis. Turkish Başlık: Sıçanlarda İyonizan Radyasyonla Oluşturulan Katarakt Üzerine Curcuminin Koruyucu Etkisi Anahtar Kelimeler: Katarakt, curcumin, iyonizan radyasyon, lipid peroksidasyonu, oksidatif stres, radioprotektif Amaç: Çalışmamızın amacı, sıçan lenslerinde iyonizan radyasyonla oluşturulan katarakt modelinde curcuminin koruyucu etkisini incelemektir. Gereç ve Yöntemler: Sıçanlar altı gruba ayrıldı. Grup 1: Kontrol, Grup 2: Dimetil sülfoksid (DMSO), Grup 3: DMSO+curcumin, Grup 4: Radyasyon, Grup 5: Radyasyon+DMSO, Grup 6: Radyasyon+DMSO+curcumin. Grup 4, 5 ve 6'ya hasar oluşturmak için iyonizan radyasyon toplam 15 Gy dozunda verildi. Curcumin (100 mg/kg), DMSO içinde çözülerek 28 gün süresince intragastrik yoldan verildi. Çalışmanın sonunda, lensler sınıflandırıldı ve çıkarıldı. Lens dokusunda antioksidan durumu değerlendirmek üzere total antioksidan, glutatyon peroksidaz (GSH-Px) enzimleri ve oksidan durumu değerlendirmek üzere malondialdehit (MDA) düzeylerine bakıldı. Bulgular: Radyasyon alan grupta %100 katarakt görüldü. Curcumin verilen grupta bu oran %40'a düştü ve grade 1 ve 2 ile sınırlıydı. Radyasyon alan grupta, kontrol grubuna göre antioxidan enzim seviyesi düştü, MDA enzim seviyesi yükseldi. Curcumin verilen grupta radyasyon grubuna göre ise anlamlı şekilde antioxidan enzim seviyesi yükseldi, MDA enzim seviyesi düştü. Sonuç: Curcumin antioksidan ve radioprotektif özelliklere sahiptir ve iyonizan radyasyona karşı koruyucu olarak değerli bir ajan olması nedeni ile antioksidan ve radioprotektör olarak radyasyon nedenli katarakt oluşumunda kullanılması önerilebilir.

The response to opioids is reduced in neuropathic pain states. We examined the effect of the combination of morphine (0.1 mg/kg) and magnesium sulfate (125 mg/kg) on behavioral signs of neuropathic pain in spinal nerve ligated rats. Administered alone, neither drug produced any effect, but the combination exerted a significant anti-allodynic effect, which was partially reversed by naloxone. These results suggest that combining low doses of magnesium sulfate with opiates might be an alternative in treating neuropathic pain, with reduced risk of side effects.

Morphine is known to release histamine from mast cells. It is also known that histamine receptors mediate some of morphine's effects on the central nervous system. The contribution of H1- and H2-receptors to the effect of morphine on maximal electroconvulsive shock in mice was investigated in the present experiments. Morphine showed a dose-dependent anticonvulsive effect, but produced spontaneous clonic convulsions at higher doses (100 mg/kg, i.p.). The anticonvulsive effect of morphine (1 mg/kg, i.p.) was antagonized by histamine H1-receptor antagonists, dimethindene (0.1 mg/kg, i.p.) promethazine (0.4 mg/kg, i.p.) and pheniramine (30 mg/kg, i.p.), and naloxone (10 mg/kg, i.p.), but not by the H2-receptor antagonist ranitidine (10-50 micrograms, i.c.v.). These results show that morphine has an anticonvulsive effect via histamine H1-receptors against maximal electroconvulsive shock in mice.

Elevated plasma asymmetric dimethylarginine (ADMA) levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that peripheral ADMA is an important contributor to opioid tolerance and dependence, by determining plasma ADMA levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to male mice, divided into groups of 3-, 6-, 9- and 10-day injection duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from carotid artery. The plasma levels of ADMA, symmetric dimethylarginine (SDMA), L: -homoarginine and L: -arginine in morphine-tolerant and -dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma ADMA and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous plasma ADMA, SDMA, L: -homoarginine and L: -arginine levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena.

Objective: The aim of this study is to evaluate the efficacy of dipyridamole in relieving the vasospasm of coronary artery bypass grafts. Material and Methods: Twenty two patients who underwent elective coronary artery bypass grafting (CABG) were admitted to the study (Men/Women: 14/8, mean age: 62.4±8.8 years). Ten samples from left internal mammary(LIMA), radial arterial (RA) and saphenous vein (SV) grafts were collected for each. The samples were transported to the vascular laboratory in 4°C Krebs solution. Submaximal smooth muscle contraction was achieved first by 10-7M of phenylephrine solution. Dipyridamole was then added, starting from a concentration of 10-9M to a concentration of 10-3.5M in two minutes intervals and half logarithmic dose increments. The concentration-response curves were obtained of the vasodilatation response relative to the begining. Results: In the LIMA graft samples, the vasodilation response to dipyridamole was 43.2±1.6% and 97.6±4.1% at concentrations of 10-6M and 10-3.5M respectively. In RA graft samples, the vasodilation response to dipyridamole was 36.3±1.8% and 95.3± 2.7% at concentrations of 10-6M and 10-3.5M respectively. In SV graft samples, however, the vasodilation response to dipyridamole was 43.2±1.4 % and 96.6± 2.2% at concentrations of 10-6M and 10-3.5M respectively. Conclusions: The amplitude of relaxation response to dipyridamole of all grafts samples were similar, without statistically significant difference among the IMA, RA and SV grafts in the in vitro tissue bath system. These results prove that dipyridamole has a potential use as a vasodilatatory drug in all graft types.

Over the years, witness security programs have developed sophisticated practices from a safe place as the only effective means of protection for the change of identity of threatened witnesses and their relocation to a new place. The success of those operations has had a positive impact on obtaining vital evidence and made witness security a significant factor in struggles to fight effectively against organized crime and terrorism. That is also why Turkey, along with the other countries, established its own witness security program, similar to WITSEC. Yet, although it has been defended arduously by the law enforcement agencies and prosecutors as one of the most valuable tools used against organized crime in the US, there is widespread criticism of the program by some scholars and the media. This research is exploratory in nature, and aims to shed light on the effectiveness of the witness security program in the fight against organized crime and terrorism. At the same time, it compares WITSEC with the witness security program of Turkey. In this context, there is one primary question brought forward: What is the impact of the witness security program on the fight against organized crime and terrorism? In order to better explore the primary research question, the following sub-research questions are examined: (a) What can be done to use the witness security program as an effective tool in the fight against cross-national terrorism and transnational organized crime? (b) How is the witness security program of Turkey differentiated from WITSEC in the context of structure, and how much influence might it have on its own criminal justice system in the future? The goal is here to make an overall contribution to the organized crime and terrorism literature. After examining the literature and the program, the research utilizes key personnel interview data. The study uses qualitative data analysis to include qualitative assessments. Policy and research implications are drawn.

Morphine has long been known to have potent effects on body temperature. It has been suggested that both N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO) pathway are involved in thermoregulation and also known to play important roles in some of morphine effects. The aim of this study was therefore to investigate the contribution of NMDA receptors and NO to the thermoregulatory effect of morphine. Morphine produced a hypothermic effect, especially at the dose of 10 mg/kg. Ketamine (5–40 mg/kg, i.p.) and NG-nitro-L-arginine-methyl ester (L-NAME, 1–100 mg/kg, i.p.) also produced hypothermic effects with their higher doses. At doses which themselves produced no effect on colonic temperature in mice, both ketamine (10 mg/kg, i.p.) and L-NAME (10 mg/kg, i.p.) enhanced the hypothermic effect of morphine (10 mg/kg, i.p.). These results further support the relationship between NO and NMDA receptors and suggest a possible role of NMDA-NO pathway in the thermoregulatory effect of morphine.

Acetylcholine receptor deficiency is the most common form of the congenital myasthenic syndromes, a heterogeneous collection of genetic disorders of neuromuscular transmission characterized by fatiguable muscle weakness. Most patients with acetylcholine receptor deficiency respond well to acetylcholinesterase inhibitors; however, in some cases the efficacy of acetylcholinesterase inhibitors diminishes over time. Patients with acetylcholine receptor deficiency can also benefit from the addition of a β2-adrenergic receptor agonist to their medication. The working mechanism of β2-adrenergic agonists in myasthenic patients is not fully understood. Here, we report the long-term follow-up for the addition of β2-adrenergic agonists for a cohort of patients with acetylcholine receptor deficiency on anticholinesterase medication that demonstrates a sustained quantitative improvement. Coincidently we used a disease model to mirror the treatment of acetylcholine receptor deficiency, and demonstrate improved muscle fatigue, improved neuromuscular transmission and improved synaptic structure resulting from the addition of the β2-adrenergic agonist salbutamol to the anticholinesterase medication pyridostigmine. Following an initial improvement in muscle fatiguability, a gradual decline in the effect of pyridostigmine was observed in mice treated with pyridostigmine alone (P < 0.001). Combination therapy with pyridostigmine and salbutamol counteracted this decline (P < 0.001). Studies of compound muscle action potential decrement at high nerve stimulation frequencies (P < 0.05) and miniature end-plate potential amplitude analysis (P < 0.01) showed an improvement in mice following combination therapy, compared to pyridostigmine monotherapy. Pyridostigmine alone reduced postsynaptic areas (P < 0.001) and postsynaptic folding (P < 0.01). Combination therapy increased postsynaptic area (P < 0.001) and promoted the formation of postsynaptic junctional folds (P < 0.001), in particular in fast-twitch muscles. In conclusion, we demonstrate for the first time how the improvement seen in patients from adding salbutamol to their medication can be explained in an experimental model of acetylcholine receptor deficiency, the most common form of congenital myasthenic syndrome. Salbutamol enhances neuromuscular junction synaptic structure by counteracting the detrimental effects of long-term acetylcholinesterase inhibitors on the postsynaptic neuromuscular junction. The results have implications for both autoimmune and genetic myasthenias where anticholinesterase medication is a standard treatment.

This study assessed the efficacy of iloprost in relieving vasospasm in coronary artery bypass grafts. Radial artery (RA), left internal thoracic artery (LITA) and saphenous vein (SV) grafts were taken from 20 patients (13 men and seven women, mean age 63.8 years [range 48 − 74 years]) scheduled to undergo coronary artery bypass grafting. Ten 3 mm vascular rings were cut from each graft and kept under tension for at least 60 min. They were kept alive with 37°C oxygenated Krebs solution. Smooth muscle contraction was achieved with phenylephrine before iloprost was administered every 2 min, starting at a concentration of 10−9 mol/l and increasing in logarithmic increments to a concentration of 10−5 mol/l. The vasodilation response to iloprost started in all samples at a concentration of 10−9 mol/l and increased with each incremental increase in iloprost concentration up to 10−5 mol/l. These data suggest that local administration of iloprost has a role in relieving graft vasospasm during harvesting and preparation for coronary artery bypass grafting.

Key points The physiological significance of the developmental switch from fetal to adult acetylcholine receptors in muscle (AChRs) and the functional impact of AChR clustering by rapsyn are not well studied.Using patch clamp experiments, we show that recovery from desensitization is faster in the adult AChR isoform.Recovery from desensitization is determined by the AChR isoform‐specific cytoplasmic M3–M4 domain.The co‐expression of rapsyn in muscle cells induced AChR clustering and facilitated recovery from desensitization in both fetal and adult AChRs. In fetal AChRs, facilitation of recovery kinetics by rapsyn was independent of AChR clustering.These effects could be crucial adaptations to motor neuron firing rates, which, in rodents, have been shown to increase around the time of birth when AChRs cluster at the developing neuromuscular junctions. Abstract The neuromuscular junction (NMJ) is the site of a number of autoimmune and genetic disorders, many involving the muscle‐type nicotinic acetylcholine receptor (AChR), although there are aspects of normal NMJ development and function that need to be better understood. In particular, there are still questions regarding the implications of the developmental switch from fetal to adult AChRs, as well as how their functions might be modified by rapsyn that clusters the AChRs. Desensitization of human muscle AChRs was investigated using the patch clamp technique to measure whole‐cell currents in muscle‐type (TE671/CN21) and non‐muscle (HEK293) cell lines expressing either fetal or adult AChRs. Desensitization time constants were similar with both AChR isoforms but recovery time constants were shorter in cells expressing adult compared to fetal AChRs (P, Key points The physiological significance of the developmental switch from fetal to adult acetylcholine receptors in muscle (AChRs) and the functional impact of AChR clustering by rapsyn are not well studied.Using patch clamp experiments, we show that recovery from desensitization is faster in the adult AChR isoform.Recovery from desensitization is determined by the AChR isoform‐specific cytoplasmic M3–M4 domain.The co‐expression of rapsyn in muscle cells induced AChR clustering and facilitated recovery from desensitization in both fetal and adult AChRs. In fetal AChRs, facilitation of recovery kinetics by rapsyn was independent of AChR clustering.These effects could be crucial adaptations to motor neuron firing rates, which, in rodents, have been shown to increase around the time of birth when AChRs cluster at the developing neuromuscular junctions.