Science topic

Morphine - Science topic

The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle.
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I want to study the effects of a pharmacological treatment (antidepressants) related to quality of life in oncologic patients. Apart from a depression diagnosis that would be a prerequisite for administering the treatment, i need another screening tool that could confirm the patient's ability to be functioning enough to give me true and valid answers later in the main tests. For this reason I am looking for a validated tool in clinical setting that could detect any cognitive impairment due to a psychiatric condition or substance induced (es. high doses of morphine).
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Hello, I'm developing a tool that can help with that, it works with id and color pigmentation areas, one of the tool's modules can help with that. I'll be happy to help.
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I want to design an aptamer for morphine by in sillico method and i need some basic sequence but i can not find them. if you have a library or know some article that can help me , please introduce me. thanks
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E-AB sensors, or electrochemical aptamer-based sensors, are a flexible type of sensing platform that can identify targets in complicated matrices quickly and reliably. But these sensors' low sensitivity has made it difficult for them to go from proof-of-concept to commercial goods. In order to bind targets and then fold for signal transduction, surface-bound aptamers need to be appropriately spaced apart. We postulated that conventionally produced electrodes produce sensing surfaces with only a portion of aptamers suitably positioned to actively respond to the target. Alternatively, we introduced a new method for immobilising aptamers that promotes microscale spacing between aptamers for the best possible target binding, folding, and signal transduction.
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Hello All,
First I want to start this discussion by thanking you for helping me with this as it is something I have been struggling to figure out.
I picked up this study from a graduate student before and now I am stumped by how to run the data using either SPSS or R (preferably R) or another recommendation. I have attached the data I am working with and as you can see it is divided into three treatment groups: Saline, 10mg/kg, 20mg/kg. By Sex: Male & Female and across three time periods: 12HR, 24HR, 36HR. I was looking at withdrawal scores and in particular certain attributes associated with withdrawal in the rat which is 11 items. What would be the best method to run this data if I want to look for effect of treatment and sex differences on the withdrawal behaviors?
Thank you again.
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2-Way MANOVA? As long as your dependent variables are gaussian normally distributed and have equal variances between groups.
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Currently, I’m studying the cellular Ca2+ responses, induced by morphine or fentanyl, of HEK293T expressing μ -receptor, in which 4μM Rhod-2-AM is loaded as a fluorescent Ca2+indicator. The Ca2+ signaling is investigated by the FLIPER PENTA (Exc. Wlength: 510-545 nm; Em Wlength: 565-625nm; Gain: 100; Exp. Time: 0.2s). As reported in many pieces of literature, the intracellular Ca2+ decreased obviously after adding cera tain concentration of morphine or fentanyl, indicating an inhibiting effect on calcium influx (A-B). However, a high and sharp peak appeared in the next few minutes, and I could not correctly interpret its biological significance by consulting the existing literature. The same phenomenon exists in all other wells (C-D). Have you ever found a similar phenomenon in your experiment? I would appreciate it if you could give me some directions.
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...and you should provide some more controls Quisheng (e.g. media only, plus media with solvent).
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Recently several babies exposed to methadone and benzodiazapines have been overly sleepy with minimal interest in feeding, extremely gassy and are over a month of age and already off morphine and clonidine treatment for NAS.
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Dear Cami,
to may no ledge there is no paper specifically address G-Tube placement in NAS. There are only prevalence studies vlbw infants, see.
Khalil, S. T. et al. (2017). Outcomes of Infants With Home Tube Feeding: Comparing Nasogastric vs Gastrostomy Tubes. Journal of Parenteral and Enteral Nutrition, 0148607116670621.
Hoogewerf M, Ter Horst HJ, Groen H, Nieuwenhuis T, Bos AF, van Dijk MWG. The prevalence of feeding problems in children formerly treated in a neonatal intensive care unit. J Perinatol. 2017;37(5):578-84.
To my knowledge opiate use or withdrawal syndrome were not systematically addressed. It would be a very interesting research question.
sincerely
Markus Wilken
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Repetitive opiate drug usage results in physical dependence which is approved by the appearance of withdrawal symptoms. withdrawal symptoms are dividing into two groups; Checked and Graded signs.
I would really appreciate it if I get guidance related to this issue.
Another issue is what are the pros and cons of using this kind of assessment?
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Hi Mahgol
I don't know about animal modelling unfortunately, but can't find any validated tool for this. You need a more behavioural approach unless taking physiological measures. Try Pinelli and Trivulzio to give you an idea of how to use a behavioural approach :
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I want to purchase some Morphine Standard for HPLC to detect Morphine rate in Papaver somniferum L. how much is need in every stage or phase?
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So, as you see that even 1 mg will be ok to make a stock solution. Maybe you can instead a ready stock solution at desired concentration.
Regards
GB
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I am currently working within ambient ionisation mass spectrometry, specifically thermal desorption APCI and looking at the linear range of my analytes using the calibration range 10-50 ppm with increments of 10 ppm. I am working in positive mode using selected ion monitoring for each analyte, as it's a single quadrupole mass spectrometer.
I have experienced a significant reduction in analyte signal for amphetamine and morphine from 10 ppm to 20 ppm. The response at 10 ppm was approximately 3.00e7; however, when I test 20 ppm the signal is circa 2.00e4 and remains as so for 30-50ppm. I am using aluminium foil as my sample swab material and when the sample is pipetted onto the surface, it disperses but the covered surface goes into the thermal desorber oven so I would expect full desorption of the analyte.
I'm stumped at this point and would appreciate any help.
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If there is no simple error in concentrations samples marking...
Does you instrument get saturated at 10 ppms? The peak is sharp?
Secondly if there is any autorange mode (ie change of detector sensitivity in case of saturation)?
Any adducts can be formed at higher concentration having different m/z?
Regards
GB
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Thanks for reviewing the animal studies of the 1970's and especially for describing the results of our early study that did not find that enriched rearing led adult rats to avoid self-selection of morphine and cocaine. Your review shows that the effects of early environment are complicated and also demonstrates the importance of caution in interpreting such studies. An alternative interpretation to that of Alexander, based on our results might suggest that too much stimulation in the early environment may lead adult animals (rats and humans) to continually expect and seek such stimulation by changing state through use of drugs. Could it be the case that children in today's world with an enormous amount of screen time (cell phones, internet, TV) may be at a disadvantage from the standpoint of susceptibility to drug use later in life?
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Andrew -- Thanks. Yes, I am a fan of the ABCD study -- had the privilege of being an NIH reviewer of the study at its inception and at its renewal this past fall. However, I think we must be careful to separate effects of screen time on brain indices (cortical thickness, etc) as ABCD data shows, and learned patterns of reward. It may be the case that youngsters who become dependent on constant stimulation require greater stimulation as adolescents and as young adults. When this is not forthcoming from normal venues (e.g., job and family) the greater stimulation history may promote drug seeking to increase stimulation (change of state) for those so accustomed to constant stimulation. Our rat data showed that young animals raised in an enriched environment with a lot of stimulation (other rats and toys in an open-field apparatus stocked with sand) were more likely to choiose cocaine/water solutions over plain water when compared to standard housing (wire cage-raised rats without companions and toys).
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Beside color marker injection, is there any pharmacological agent (beside morphine) that induce a particular phenotype (morphine Straub tail) in mice? thanx in advance Roland
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I agree. One day!
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I'm currently studying perinatal opioid exposure in rats. We've been using morphine pellets, but are considering switching to osmotic minipumps. However, we want to ensure that our dosing is as clinically relevant as possible. Is there a formula or suggested conversion for human effective morphine doses to their equivalent rat dose? I've been considering both equivalent plasma levels and equianalgesic doses, but I wondered if the data already exists somewhere. Thanks!
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Nair, A. B., & Jacob, S. (2016). A simple practice guide for dose conversion between animals and human. Journal of basic and clinical pharmacy, 7(2), 27.
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We synthesized highly purified thalidomide by ourselves and we have treated many patients with malignancies using thalidomide and celecoxib with good efficacy. But in Shizuoka Prefecture, I was ordered to cooperate the recall of thalidomide by the President of Shizuoka Prefecture(=Shizuoka Ken) because thalidomide synthesis is against the Law.. Our works are cited on many famous medical journals and textbook overseas. Japanese Government ordered not to conduct clinical trials for advanced patients with solid tumors. Because thalidomide is the dangerous drug and difficult to keep the patient safety. Moreover, many advanced cancer patients are refused to treat more after standard chemotherapy at Shizuoka Cancer Center, even if they could be estimated to recover with thalidomide and celecoxib. Please cooperate to help Japanese advanced cancer patients save their lives from Shizuoka Concentration Cancer Center. Without your helps, they have to die with the cease of respiration after injections of overdose morphine hearing the stream sound of high volume oxygen.
The present President of Shizuoka Prefecture is Heita Kawakatsu and Shizuoka Cancer Center is Ken Yamaguchi.
Masato Hada
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The reply from Shizuoka Cancer Center was irresponsible and they try to conceal their mistakes without writing even the name of the person in charge.
Feb 18, 2019
You reached the Shizuoka Cancer Center with your previous email to the attention of Dr. Hada.
However, we are afraid that there is no "Dr. Hada" here.
Apparently you sent us the email by mistake.
Would you please check your record again and forward it to the right email address?
Thank you.
Best regards,
Shizuoka Cancer Center
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When digested, AI milk releases beta-casomorphin7 (BCM7), an opioid with a structure similar to that of morphine that some studies have linked with autism. Does anyone have information on the mechanism of BCM7 formation?
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Hello... Anthony Foris
In vitro studies have shown that, the bioactive peptide β-casomorphin-7 (BCM‐7) is produced by the successive gastrointestinal proteolytic digestion of β-casein A1, but such cases were not seen in β-casein A2 type milk.
Kindly see these two articles:
Pictorial representation made by me is also in attachment.
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Hi guys
Does any one have the full text article for " Identification of Possible Binding Sites for Morphine and Nicardipine on the Multi-drug Transporter P-Glycoprotein Using Umbrella Sampling Techniques "???
Authors:
  • Nandhitha Subramanian
  • Karmen Condic-Jurkic
  • Alan E Mark
  • Megan L. O'Mara
Thanks in advanced
Fatemeh
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Thanks alot.
Now I am really happy.
god bless you..
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Considering the small size of the molecules, an association with bigger immunogenic protein is necessary (BSA, KLH, TT).
1- is a spacer necessary for a better recognition of the antigen (thinking of succinic acid)?
2- what are the best animal models to be chosen (mice, rabbits or others)?
3- After antibody purification, what is the stability of the retrieved antibodies? is it possible to use them for other detection methods (ELISA, WB etc)?
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It usually ia advantageous to add a spacer. We have used from 2-4 glycine molecules.
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Some patients on opiate or opioid analgesics paradoxically react with hyperactivity, verbosity and insomnia. As a student (more than 50 years ago) this was demonstrated during the pharmacology lectures bij injecting a cat with morphine and show it a white mouse, whereupon the cat panicked and jumped up and down its cage. Our pharmacology professor then explained that 'a small percentage of the human population reacted like cats', and indeed, this is reported incidentally by patients.
Can anybody explain the incidence and mechanism of this paradoxical effect?
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Frederik A De Wolff 45.02  Leiden University
What is the incidence and mechanism of the excitatory effect of opiates in some humans?
Some patients on opiate or opioid analgesics paradoxically react with hyperactivity, verbosity and insomnia. As a student (more than 50 years ago) this was demonstrated during the pharmacology lectures bij injecting a cat with morphine and show it a white mouse, whereupon the cat panicked and jumped up and down its cage. Our pharmacology professor then explained that 'a small percentage of the human population reacted like cats', and indeed, this is reported incidentally by patients.
Can anybody explain the incidence and mechanism of this paradoxical effect?
What is the incidence and mechanism of the excitatory effect of opiates in some humans?. Available from: https://www.researchgate.net/post/What_is_the_incidence_and_mechanism_of_the_excitatory_effect_of_opiates_in_some_humans [accessed Jun 6, 2017].
 Charles Schaffer & I found evidence that nearly one-third of bipolar patients when taking mu-opiates would have a manic-like reaction that might last a day or two.  In some cases this was the subject[s first manic episode.  There is evidence of interaction between dopamine and opiate system and perhaps a large subset of bipolar patients might be overly sensitive to the DA-opiate interaction.  We published one report but not the second, which had incidence around 35 percent.  Thanks you.Tom Nordahl UCD
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I am looking for a protein that it's conformation changes  specifically by  binding morphine molecule to it. 
Is there such protein? or are there any software change a protein to that bind specifically to morphine?
Thank you
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Go to the PDB website (RCSB.org). Click on "ligand."  Enter "morphine."   It should output a list of proteins that bind morphine.  Suppose protein P binds morphine. Download the structure of P alone (no bound ligands) and P with bound morphine. Compare the two structures by doing a 3D superimposition (a.k.a. superposition) of their corresponding proteins parts.  You can visually inspect the two superimposed structures and see where the greatest departures are.  You can also calculate the RMSD of the superposed structures.
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Eleonore Dorothea Auguste Henriette von Rettberg was the wife of Friedrich Sertürner, who isolated the first alkaloid in 1804; morphine from opium. Did Frau Sertürner die of a morphine overdose? Any leads would be most welcome.
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This question is for the people practicing outside USA because in USA this number is quite high. I am doing some international work andI am just interested in OB anesthesia practise outside USA.
When you provide anesthesia for Cesarean Section what percentage of your patients receives spinal or epidural morphine?
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I often use morphine in cesarean section. I used to utilize larger doses, up to 100 micrograms, but nowadays, I usually utilize 40-60 micrograms, varying according to total body mass index and we see much fewer side effects, comparing to its benefits in pain control. 
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This is questions for practitioners from outside USA, because morphine chloride is not available in USA
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Usually, intrathecal infusion pumps used as drug morphine. They have very good results if handled properly.
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The WHO analgesic ladder has weak opiods like codeine and tramadol, however they are expensive and not easily available. Do you have any experience on the use of low dose morphine instead of the weak opiods
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Codeine, which in itself possesses no analgesic activity, is metabolized to morphine by CYP450 2d6, which is expressed in subnormal levels in 5-10% of humans. They will not benefit from codeine. One could reasonably argue if there is any advantage in using a drug with such a high failure rate at all.
Also, some patients are rapid metabolizers and will experience high plasma morphine concentrations. This had led to at least two deaths of babies nursed by codeine users.
The rational choice, as Francis suggests, is to use morphine in lower doses. Same or better effect, fewer side effects, less risk to the patient.
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The Driving Authority in the UK (DVLA) has set a limit for morphine of 80 mcg/litre plasma concentration. Does anyone have any figures giving an idea what this equates to in dose terms for palliative patients?
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Someone needs to study plasma levels of people who are currently taking oral morphine.
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Have you ever heard of Midazolam being used in conjunction with morphine for the treatment of MI chest pain, and associated synergistic benefits?
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Midazolam may cause serious breathing problems. It should be avoided in conjunction with morphine for the treatment of acute coronary syndromes. There may be a special sensitivity.
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I am studying research surrounding the use of intranasal analgesia (fentanyl or diamorphione) for paediatric pain in pre-hospital settings as opposed to IV/IM morphine or other weaker analgesics. Any paediatric pain scoring models would also be of assistance, or research surrounding the above topics. 
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The PICHFORK (Pain in Children Fentanyl or Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine and Fentanyl for the Relief of Moderate to Severe Pain in Children With Limb Injuries.
Graudins A1, Meek R2, Egerton-Warburton D2, Oakley E3, Seith R4.
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Methadone maintenance is in the patients perspective a quiet "boring" drug. We think that not only cocaine is often used in high dose maintenance, but also alcohol (carbonic acid + alcohol = "cick"). My question is:
Does anybody know wheher there are combination maintenance programs with fast acting morphine in daytime and low methadone for the night?
regards
c. jellinek
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I agree with Dr. Dillon that methadone is quickly becoming obsolete for patients with Opioid Use Disorder (DSM Dx 304.xx), but for different reasons.  Methadone, WHEN ADMINISTERED PROPERLY, remains the "gold standard" for maintenance treatment.  The problem is, it's very expensive to administer it properly - you need drugs-of-misuse screening tests, complementary therapy - in other words, a very well-run methadone clinic - these are few and far between.  I have not observed the "drool effect" Dr. Dillon references in PROPERLY DOSED PATIENTS in top-decile clinics, which I have visited.  On the other hand, patients with too high a dose of a strong opioid will always drool, nod, etcetera.  
Buprenorphine is safer and more convenient for the patient, and far less mis-usable amongst pts with even mild opioid tolerance.  Speaking of safety, and to answer the original question: no!  Not only do you risk hyperalgesia but also you risk RESPIRATORY DEPRESSION AND MORTALITY if you COMBINE MORPHINE AND METHADONE.  This is a VERY VERY RISKY MAINTENANCE STRATEGY (mixing long-acting and short-acting opioids) and even assuming it's all done inpatient, the risks of something going wrong, in my option, outweigh any possible benefits.  
Best option: switch to buprenorphine.  Worst option, if you feel you MUST augment morphine (again, not suggesting you do this): use something a little less RD (respiratory depressive) than morphine, such as hydrocodone (fast acting, high bioavailability through oral administration).  
Also, with all due respect, maintenance medications are supposed to be "quiet BORING drugs" and patients should get used to it.  The meds (bupe and methadone) are supposed to eliminate the craving for opioids, and NOT act as a euphorigenic.   
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Dexmedetomidine is used as an adjuvant to intrathecal  local anesthetic                     (Bupivacaine/ Ropivacaine ). Does it help in prolonging duration of spinal anesthesia? How would you rate it on comparison to fentanyl/ morphine?
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Have never used it, coz this is the place where it can be carried to CNS and its vital tissues directly. However, in the epidural route and peripheral blocks the absorption characteristics are variable. But free accessibility of this drug to CNS structures while floating in CSF has not been studied extensively and mainly Indian studies are available only. Even the dose calculation is little weird when it is used intrathecally. Concerns from FDA are likely to come up soon regarding its intrathecal use.
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Respiratory depression
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I have experience of an IV dose as low as 5mg causing respiratory depression requiring ICU admission and intubation as the junior medic did not check/realise that the patient had chronic renal failure.
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I see many "drug babies" born to women in their late 30's. A majority of the women are using Subutex (Suboxone) or Methadone as a means to come off other drugs. Babies usually score 6-10 in the first 24 hours but can jump as high as 44 in the 24-48 hour range depending how much mom was getting. We want the babies to be on high calorie formula, but should we use mom's breast milk to dose the baby instead of the morphine?
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We use AAP guidelines and consider morphine if modified Finnegan scores are persistently above the 8 to 10 range but it is important to consider that the mother may have been a polysubstance user. Morphine has been shown to be associated with a lower incidence of seizures in neonatal abstinence syndrome due to opiate withdrawal but its predecessor phenobarbitone is still recommended in neonatal abstinence symptoms  due to other substances. As in most conditions it comes down to the risk/benefits of the condition versus those of the treatment. Certainly the small amounts of opiates in breast milk  help alleviate withdrawal however the volume of breast milk is not very high in the first few days and the autonomic effects of withdrawal such as diarrhoea, together with the increased caloric usage by crying, restlessness and tachypnoea make dehydration and weight loss a real problem for those born to mothers taking high dose opiates. Allowing the baby to withdraw more slowly by using morphine helps alleviate this but one needs to be careful of possible respiratory depression if it is used in high doses and of the short half-life of morphine making it often necessary to wean outpatient doses over several weeks.
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In terms of analgesic effects.
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Hi Zhuoyang,
have a look to this paper. Maybe, it can help you
cheers
Contemp Top Lab Anim Sci. 2000 Mar;39(2):8-13.
The magnitude and duration of the analgesic effect of morphine, butorphanol, and buprenorphine in rats and mice.
Gades NM1, Danneman PJ, Wixson SK, Tolley EA.