Ketamine is rapidly metabolized in the human body to a variety of metabolites, including the hydroxynorketamines. At least two hydroxynorketamines have significant antidepressant action in rodent models, with limited action against the N-methyl-d-aspartate (NMDA) receptor. The synthesis of 12 hydrox …The largest real-world study to date showed that ketamine intravenous therapy (KIT) may effectively relieve depression and suicidal ideation. Ketamine is an FDA-approved anesthetic...Ketamine caused a transient change in CBF; there was increased brain function in the prefrontal brain regions and decreased brain function in the hippocampal, visual, and parietal regions. Ketamine induced hyperconnectivity in hippocampal networks vulnerable to mood and cognitive disorders.Ketamine analogs have the potential advantage of retaining the efficacy of ketamine while limiting unwanted side effects. Commercial Applications Further clinical work with these ketamine analogs could establish these as effective treatments for pain, depression, anxiety, and related disorders.Feb 12, 2024 · Print. Ketamine is not extracted from a plant like cocaine, caffeine, or THC — nor can it be synthesized from store-bought chemicals like crystal meth. It was first created in 1962 by Dr. Calvin Stevens — a researcher at Parke-Davis Laboratories. Ketamine production requires specific precursor chemicals, high-tech laboratory equipment, and ... Jul 16, 2021 · Purpose of Review While ketamine’s analgesia has mostly been attributed to antagonism of N-methyl-d-aspartate receptors, evidence suggests multiple other pathways are involved in its antidepressant and possibly analgesic activity. These mechanisms and ketamine’s role in the nociplastic pain paradigm are discussed. Animal studies demonstrating ketamine’s neurotoxicity have unclear human ... A novel strategy for the asymmetric synthesis of (S)-ketamine using (S)-tert-butanesulfinamide and 1,2-cyclohexanedione. We present a novel asymmetric synthesis route for synthesis of (S)-ketamine using a chiral reagent according to the strategy (Scheme 1), with good enantioselectivity (85% ee) and yield. In this….It is reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels and a series of new analogues were designed and synthesized. Ketamine is an analgesic/anesthetic drug, which, in combination with other … Synthesis of Ketamine.pdf - Free download as PDF File (.pdf), Text File (.txt) or read online for free. Scribd is the world's largest social reading and publishing site. Oct 3, 2017 · The one study to investigate dopamine synthesis capacity found ketamine increased dopamine synthesis, although it used an anaesthetic dose. 36 Interestingly, both anaesthetic 36 and sub ... This synthesis has less step than classical Ketamine synthesis from cyclopentyl bromide and o-chlorobenzonitrile and a little bit bigger yield. Moreover, you can ship 2-(2-Chlorophenyl)-2-hydroxycyclohexanone as legal substance overseas.1-bromocyclopentyl-(o-chlorophenyl)-ketone (CAS 6740-86-9) is commercially available. It is being sold in forms of white powder or brown oil. You mentioned “This bromoketone is unstable and must be used immediately”, if that’s the case then how do …In a round bottom flask, 2-hydroxy-2-(2-chlorophenyl)-1-cyclohexane-N-methylimine (5.90 g, 25 mmol) was added to 120 mL of decaline. The mixture was stirred at 170°C for 4 h. The organic product was extracted with HCl (0.1 M). Then the reaction mixture was neutralized with … See moreIt's one of the most closely guarded syntheses in pharmaceutical history, it's very unlikely. Here's the chemistry you need to do just to create an analogue of Ketamine . Anyone purporting to be freely distributing the entire synthesis of ketamine is to be regarded with healthy skepticism. A walk in the park!May 7, 2020 · To test the hypothesis that sub-chronic ketamine administration leads to increased dopamine synthesis capacity, mice were injected once daily with ketamine (30 mg/kg) or saline for 5 consecutive days. The Insider Trading Activity of pereira ronaldo on Markets Insider. Indices Commodities Currencies StocksKetamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients …Jun 4, 2012 · Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine …Psychedelic startups want to make psilocybin, ketamine and other substances more mainstream, but how are investors approaching this space? In professional sports, player-coaches ca...Abstract. The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with psychodysleptic, hallucinogenic and dissociative properties. Following the first administration of ketamine to humans in 1964 in Jackson prison (Michigan, USA), …Nevertheless, a nasal preparation of (S)-ketamine has proven effective in phase 3 clinical trials and received FDA approval in March, 2019. In addition, the discovery of the rapid actions of ...Ketamine may also exert its effects by selectively inhibiting extrasynaptic NMDARs whose activity is associated with excitotoxicity through mTORC1 inhibition of protein synthesis (Miller et al. 2014).Apr 10, 2013 · Because of the severe psychodysleptic effects of cyclohexamine, further research in the 1960s ultimately led to the synthesis and development of ketamine (CI-581, 2-O-chloro-phenyl-2-methylamino-cyclohexanone, Ketalar ®). First clinical studies were published in 1965 3. Ketamine demonstrated a lower and shorter effect than PCP, but the ... Ketamine [2- (2-chlorophenyl)-2- (methylamino)cyclohexanone] is a dissociative anaesthetic, first developed in 1963 by Parke-Davis. It finds widespread application in the treatment of battlefield injuries, and in emergency departments for use in children. In recent times the clinical interest in ketamine has increased due to the positive …Methamphetamine. Methamphetamine [note 1] (contracted from N- methylamphetamine) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. [22] Methamphetamine was discovered in 1893 and exists as two ...Protein synthesis is a biological process that allows individual cells to build specific proteins. Both DNA (deoxyribonucleic acid)and RNA (ribonucleic acids) are involved in the p...Ketamine activates mTORC1 protein synthesis in the PFC and hippocampus (Li et al., 2010; Paul et al., 2014; Adaikkan et al., 2018; Abdallah et al., 2020). Antidepressant dose of ketamine rapidly and transiently activates the mTOR signaling, as …A synthesis method of ketamine drug intermediate cyclopentene comprises steps as follows: 1.56 mol of nickel oxide, 1.3 mol of cyclopentylamine, 1.6-1.9 mol of a 1-nitrotoluene solution and 300 ml of oxalic acid are added to a tubular reactor, the reaction temperature is increased to 270-280 DEG C, the mixture reacts for 90 …Mar 26, 2022 · High Yielding Continuous-Flow Synthesis of Norketamine | Organic Process Research & Development. PREV. High Yielding Continuous-Flow Synthesis of … A synthesis method of ketamine drug intermediate cyclopentene comprises steps as follows: 1.56 mol of nickel oxide, 1.3 mol of cyclopentylamine, 1.6-1.9 mol of a 1-nitrotoluene solution and 300 ml of oxalic acid are added to a tubular reactor, the reaction temperature is increased to 270-280 DEG C, the mixture reacts for 90-120 min, is heated to 300-310 DEG C and continuously reacts for 50-70 ... CGNSF: Get the latest Cognetivity Neurosciences stock price and detailed information including CGNSF news, historical charts and realtime prices. Ketamine One, a Canada-based healt...Feb 20, 2021 · Ketamine can be efficiently administered via multiple routes, including oral, sublingual, intranasal, intramuscular, intraosseous, rectal, and subcutaneous routes, but the highest bioavailability and fastest onset are achieved by intravenous administration [35, 38].At present, ketamine is used in emergency units for …Oct 7, 2023 · Synthesis of Ketamine.pdf - Free download as PDF File (.pdf), Text File (.txt) or read online for free. Scribd is the world's largest social reading and publishing site.Feb 20, 2017 · Introduction. Ketamine is a synthetic, non-barbiturate, injectable dissociative anaesthetic first synthesized by Calvin Stevens of the Parke-Davis Pharmaceutical Company in 1962 (Ann Arbor, Michigan) while searching for an alternative to the potent hallucinogenic agent phencyclidine [ 1, 2 ]. Due to its quick onset and short duration of action ... The history of ketamine begins in the 1950s at Parke-Davis and Company's laboratories in Detroit, Michigan, USA. ... Maddox, a chemist, discovered a process which led to the synthesis of phencyclidine or PCP [N-(1-phenyl-cyclohexyl)-piperidine] on 26 March ...Inflation is a real issue. Luckily, some credit cards can provide perks and a strong return on spending — either of which can help you beat inflation. Here are the cards we're usin...Ketamine ranks among the most basic pharmacologic tools of the anesthesiologist. Approved in 1970 as an anesthetic agent derived from phencyclidine, the drug quickly proved its worth in battlefield settings where maintenance of hemodynamic stability was a prime requirement.1 To this day the drug is valued for use in unstable … An efficient asymmetric synthesis of (S)-ketamine (esketamine) based on catalytic enantioselective transfer hydrogenation of cyclic enone and [3,3]-sigmatropic rearrangement of allylic cyanate to isocyanate is described. The catalytic asymmetric route afforded esketamine (99.9% ee) in 50% overall yield over four steps and forms the basis for the future development of the drug substance ... May 7, 2020 · To test the hypothesis that sub-chronic ketamine administration leads to increased dopamine synthesis capacity, mice were injected once daily with ketamine (30 mg/kg) or saline for 5 consecutive days. Two optional ketamine experiences (intramuscular and sublingual) supported by a fellow trainee and contingent upon medical approval. KAP and psychedelic medicine preparation and integration. Guiding clients through non-ordinary states of consciousness.Scheme 1. Synthesis of ketamine alkyl esters; Reagents and conditions: (i) Br(CH2)2CO2i ...Synthesis of Ketamine (2) Ketamine is more difficult to synthesize than the previously considered PCP derivatives. Although it is currently a popular and common drug on the illicit market, it is obtained exclusively by diversion of commercial sources rather than synthesis.Amy Lee Bredlau, Rajbala Thakur, David Nathan Korones, Robert H. Dworkin, Ketamine for Pain in Adults and Children with Cancer: A Systematic Review and Synthesis of the Literature, Pain Medicine, Volume …Sep 11, 2014 · Synthesis of seven-membered ring analogues of ketamine was studied with two strategies. In the first approach a sequence of five reactions was used which previously applied for ketamine synthesis. This strategy led to formation of 1-[(2-chlorophenyl)(methylimino)methyl]cyclohexan-1-ol as a precursor for the target molecule. In the second approach, we have designed and attempted to synthesize a ... An efficient asymmetric synthesis of (<i>S</i>)-ketamine (esketamine) based on catalytic enantioselective transfer hydrogenation of cyclic enone and [3,3]-sigmatropic rearrangement of allylic cyanate to isocyanate is described. The catalytic asymmetric route afforded esketamine (99.9% ee) in 50% ove …Dec 14, 2023 · In addition, a novel process for the synthesis of ketamine precursor 2-chlorophenyl cyclopentyl ketone from cyclopentanone p-toluenesulfonylhydrazone and 2-chlorobenzaldehyde was validated. This is the first report to uncover this novel process for the synthesis of 2-chlorophenyl cyclopentyl ketone and can be used to …Apr 2, 2023 · Abstract. Ketamine [2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one] has been used in both veteri-nary and human medicine. In this research, a new and efficient protocol has been developed for the synthesis of ketamine, by using hydroxy ketone intermediate. Synthesis of this drug has been done in five steps. …Ketamine [2- (2-chlorophenyl)-2- (methylamino)cyclohexanone] is a dissociative anaesthetic, first developed in 1963 by Parke-Davis. It finds widespread application in the treatment of battlefield injuries, and in emergency departments for use in children. In recent times the clinical interest in ketamine has increased due to the positive … 9. alpha-bromo- (o-chlorophenyl)-cyclopentyl ketone. 40g ketone is dissolved in 70mls CCl4 and with cooling in snow it is added into a soln of 48g dioxane dibromide in 50mls dioxane, and stirred at RT for 30mins. Then 30mls water are added and the soln is washed with NaHCO3 aq. until neutral. Jun 29, 2023 · This is the first report to uncover this novel process for the synthesis of 2-chlorophenyl cyclopentyl ketone and can be used to increase awareness among law enforcement officers and forensic practitioners about these novel starting materials for the synthesis of ketamine. Mar 19, 2019 · A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The … 3:Heat solution to 180 C hold on 30 min. 4:Cool the solution to 0 C hold on 2 h filter or centrifugate to separate liquid an dry component. 5 ry the Compound at 80 C for 6 h now appears brown color. 6:Add 10 times weight of water heat to 70 C add 5% weight of active carbon. stir 30 min. 7:Filter three times to remove the carbon. Mar 17, 2021 · Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index …A synthesis method of ketamine drug intermediate cyclopentene comprises steps as follows: 1.56 mol of nickel oxide, 1.3 mol of cyclopentylamine, 1.6-1.9 mol of a 1-nitrotoluene solution and 300 ml of oxalic acid are added to a tubular reactor, the reaction temperature is increased to 270-280 DEG C, the mixture reacts for 90 …In 2017, Zhang and co-workers reported a copper-assisted direct nitration of cyclic ketones with CAN, which enabled a short synthesis of ketamine (4) and norketamine (5) (Scheme 1). 26 In 2019 ...Jul 24, 2023 · Abstract. Ketamine is an open channel blocker of ionotropic glutamatergic N -Methyl- D -Aspartate (NMDA) receptors. The discovery of its rapid antidepressant effects …Feb 20, 2021 · Finally, the molecular determinants of ketamine’s action are thought to converge on the mTOR complex, which is involved in cellular protein synthesis and metabolism. As demonstrated by Li et al. (2010), subanesthetic doses of ketamine increase levels of synaptic protein and formation of dendritic spines in the prefrontal cortex of rats. Mar 6, 2022 ... D., was consulted to help synthesize a new phencyclidine (PCP) derivative. Phencyclidine was being used as an anesthetic medication at the time ... 9. alpha-bromo- (o-chlorophenyl)-cyclopentyl ketone. 40g ketone is dissolved in 70mls CCl4 and with cooling in snow it is added into a soln of 48g dioxane dibromide in 50mls dioxane, and stirred at RT for 30mins. Then 30mls water are added and the soln is washed with NaHCO3 aq. until neutral. Mar 17, 2021 · Replicated international studies have underscored the human and societal costs associated with major depressive disorder. Despite the proven efficacy of monoamine-based antidepressants in major depression, the majority of treated individuals fail to achieve full syndromal and functional recovery with the index …Mar 19, 2019 · A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The …May 15, 2019 ... In this very competitive context, the team with the Center for Integrated Technology and Organic Synthesis (CiTOS, UR MolSys) under the ...Here are the best gas station and third-party loyalty programs plus a few stacking opportunities to use two or more of these programs on a fill-up. Editor’s note: This post has bee...Improving Ketamine Mileage: Ideal ketamine treatment is in a safe and supervised setting. This article highlights some simple ways to get the most out of every ketamine treatment. The American Society of Ketamine Physicians, Psychotherapists, and Practitioners is a non-profit group of professionals dedicated to the safe clinical use of Ketamine for …Amy Lee Bredlau, Rajbala Thakur, David Nathan Korones, Robert H. Dworkin, Ketamine for Pain in Adults and Children with Cancer: A Systematic Review and Synthesis of the Literature, Pain Medicine, Volume … Today, ketamine has become an attractive substance for recreational use, gradually emerging from alternative techno circles to spread to more commercial party scenes. These elements represent a public health concern, associated with the risk of developing new chemically synthesized analogues, the harmful effects of which are still little known. Feb 12, 2024 · Notably, important precursors to ketamine synthesis like “hydroxylimine” (1-[(2-chlorophenyl)-N- (methylimino) methyl]cyclopentanol) and o-chlorophenyl cyclopentyl ketone are difficult to obtain. However, views among regulators began to shift in 2015 when China reported to the Commission on …Jul 24, 2023 · Ketamine is an open channel blocker of ionotropic glutamatergic N-Methyl-D-Aspartate (NMDA) receptors. ... specifically rapid translation and synthesis of BDNF protein in hippocampal dendrites . Ketamine analogs have the potential advantage of retaining the efficacy of ketamine while limiting unwanted side effects. Commercial Applications Further clinical work with these ketamine analogs could establish these as effective treatments for pain, depression, anxiety, and related disorders.Oct 1, 2020 · This imine is synthesized from the bromination of 2-chlorophenyl cyclopentyl ketone with toxic bromine and then reaction with methy …Abstract. Ketamine is a non-competitive channel blocker of N -methyl- d -aspartate (NMDA) receptors 1. A single sub-anaesthetic dose of ketamine produces rapid (within hours) and long-lasting ...Feb 20, 2021 · Abstract. Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More …1356009 - R15880. Valid Use Date. Current. Country of Origin*. India. Material Origin *. Chemical Synthesis. Lot No. R083G0. USP Certificate or Product ...Jun 26, 2023 · In this study, we developed an enhanced and efficient kilogram-scale synthesis method for ketamine hydrochloride. We discovered that using N-bromosuccinimide (NBS) instead of HBr/H2O2 improved the conversion rate of the bromination reaction from 88% to 99% and led to a milder and steadier reaction. Besides, CH3NH2/K2CO3 was used in the methylamination reaction to shorten the reaction time from ... Get ratings and reviews for the top 7 home warranty companies in The Crossings, FL. Helping you find the best home warranty companies for the job. Expert Advice On Improving Your H...Ketamine was first synthesized in 1962 by Calvin Stevens at Parke-Davis Co (now Pfizer) as an alternative anesthetic to phencyclidine. It was first used in humans in 1965 by Corssen and Domino and was introduced into clinical practice by 1970. Ketamine is frequently described as a “unique drug” because it shows hypnotic (sleep-producing ...An improved synthesis of (S)-ketamine (esketamine) has been developed, which was cost-effective, and the undesired isomer could be recovered by racemization. Critical process parameters of each step were identified as well as the process-related impurities. The formation mechanisms and control strategies of most impurities were first …A medicinal chemist, V. Harold Maddox, discovered a new chemical organic Grignard reaction, which led to the synthesis of phencyclidine (later given the clinical investigation number CI-395) on March 26, 1956. 12 …Feb 20, 2024 ... These plants, often native to specific regions, possess the remarkable ability to synthesize ketamine. The synthesis of this compound in plants ...These data demonstrate that ketamine reduced both 5-HT synthesis and metabolism in vivo. Since ketamine did not affect brain tryptophan levels nor did it inhibit 5-HT in vitro, the reduction of 5-HT turnover following ketamine administration appears to be a neuronal, adaptive phenomenon possibly occurring in response to a blockade of 5-HT uptake by …Mar 6, 2022 ... D., was consulted to help synthesize a new phencyclidine (PCP) derivative. Phencyclidine was being used as an anesthetic medication at the time ...Ketamine is a structural analog of the dissociative anesthetic and recreational drug phencyclidine (PCP).[1] Similar to phencyclidine, ketamine causes analgesia and amnesia without the cardiovascular and respiratory depression associated with common anesthetics.[1] Originally called CI-581, ketamine has one-tenth the …Feb 20, 2021 · Abstract. Over the past 50 years, ketamine has solidified its position in both human and veterinary medicine as an important anesthetic with many uses. More … Abstract. Ketamine [2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one] has been used in both veteri-nary and human medicine. In this research, a new and efficient protocol has been developed for the synthesis of ketamine, by using hydroxy ketone intermediate. Synthesis of this drug has been done in five steps. At first, Our studies show ketamine blocks synaptic NMDA receptors involved in spontaneous synaptic transmission, which deactivates calcium/calmodulin-dependent kinase eukaryotic elongation factor 2 kinase (eEF2K), resulting in dephosphorylation of eukaryotic elongation factor 2 (eEF2), and the subsequent desuppression of brain-derived neurotrophic ...The latest research on Leucine Supplements. Expert analysis on potential benefits, dosage, side effects, and more. Leucine is most often used for . Leucine is a branced-chain amino...
Ketamine activates mTORC1 protein synthesis in the PFC and hippocampus (Li et al., 2010; Paul et al., 2014; Adaikkan et al., 2018; Abdallah et al., 2020). Antidepressant dose of ketamine rapidly and transiently activates the mTOR signaling, as …. The cincinnati enquirer
Ketamine may also exert its effects by selectively inhibiting extrasynaptic NMDARs whose activity is associated with excitotoxicity through mTORC1 inhibition of protein synthesis (Miller et al. 2014).The Cyberspace Administration of China wants deep synthesis providers to seek user permission before making their deepfake China’s cyberspace regulator is cracking down on deepfake...Dec 1, 1990 · A new process of ketamine synthesis from 2- (2-chlorophenyl)-2-nitrocyclohexanone proposed by analyzing drug materials and chemicals seized in Taiwan. Because of its hallucinogenic and dissociative effects, ketamine is often abused for recreational purposes. Thus, the seizure of ketamine manufacturing … The Origin of Ketamine. Since its synthesis in a Detroit laboratory nearly six decades ago, ketamine has proven to be a complex medication with unusual properties, heterogeneous, interconnected mechanisms, and diverse, sometimes contested, clinical uses. Mar 15, 2001 ... EU acts on rising concern over synthetic drugs GHB and ketamine ... The EU today responded to rising concern over the misuse of GHB and ketamine.Synthesis of ketamine involves four steps, as depicted in Scheme 1 [1]. In this strategy, 1-(2-chlorobenzoyl)cyclopentane, 3, prepared by reaction of 2-chloroben-zonitrile, 1, and cyclopentylmagnesium bromide, 2, was brominated to give (1-bromocyclopentyl)(2-chlorophenyl)methanone (4). Bromoketone 4, on reaction with an aqueous solution of ...Ketamine is rapidly metabolized in the human body to a variety of metabolites, including the hydroxynorketamines. At least two hydroxynorketamines have significant antidepressant action in rodent models, with limited action against the N-methyl-d-aspartate (NMDA) receptor. The synthesis of 12 hydrox …Dec 14, 2023 · In addition, a novel process for the synthesis of ketamine precursor 2-chlorophenyl cyclopentyl ketone from cyclopentanone p-toluenesulfonylhydrazone and 2-chlorobenzaldehyde was validated. This is the first report to uncover this novel process for the synthesis of 2-chlorophenyl cyclopentyl ketone and can be used to …Synthesis of Ketamine (2) Ketamine is more difficult to synthesize than the previously considered PCP derivatives. Although it is currently a popular and common drug on the illicit market, it is obtained exclusively by diversion of commercial sources rather than synthesis.The one study to investigate dopamine synthesis capacity found ketamine increased dopamine synthesis, although it used an anaesthetic dose. 36 Interestingly, both anaesthetic 36 and sub ...Ketamine is extracted with 20% HCl. Acidic extract is basified and extracted with DCM. Solvent is removed giving the product as an oil that ...Ketamine for opioid-resistant pain in palliative care. Ketamine is widely used as a third-line drug for cancer pain, when the pain has not responded to opioid in combination with drugs such as nonsteroidal anti-inflammatory drugs, amitriptyline, and gabapentinoids. Published case reports demonstrate that ketamine is used for refractory …May 15, 2019 ... In this very competitive context, the team with the Center for Integrated Technology and Organic Synthesis (CiTOS, UR MolSys) under the ...Pharmacokinetics Ketamine is available in multiple formulations, of which the intravenous and intranasal routes have the most compelling evidence of efficacy in TRD. As summarized in Table 2, the bioavailability of ketamine differs as a function of route of delivery, and a gradient of bioavailability is observed (i.e., intravenous > intramuscular > …Flagstones are a popular choice for walkways and patios because of their natural beauty and durability. Stefan Grunkemeier from Simply Rocks shows us how to install one. Flagstones....