Morphine Haloperidol

Buydens P, Govaerts J, Velkeniers B, Finne, Vanhaelst L (1988) The effect of bombesin on basal, a-methyl-p-tyrosine, haloperidol, morphine, bremazocine and stress-induced prolactin secretion. Life Sci 43 1755-1760. 

Electrochemical detectors can be used in the oxidative mode for a wide range of drugs, including cannabinoids, haloperidol, morphine, paracetamol, phenothiazines, salicylic acid, and tricyclic antidepressants. Operation in the reductive mode is more difficult as dissolved oxygen must be removed from the eluent (K. Bratin et al, J. liq. Chromat., 1981,, 1777-1795). Reductive applications include chloramphenicol and benzodiazepines. 

Fig. 20.11. Substrate quality obtained by comparing basolateral-to-apical with apical-to-basolateral transport of substrates in polarized cell monolayers of MDR1-transfected cell lines [86] plotted versus (A) the log of the air/water partition coefficient, or (B) H-bond energy (arbitrary units, EUh cf. text). Units of the air/ water partition coefficient were [M ]. Compound (concentrations in Ref. [86] in brackets) were clozapine (50 nM) (1) cyclosporin A (2 tM) (2) daunorubicin (3) dexamethasone (2 tM) (4) digoxin (2 pM) (5) domperidone (2 pM) (6) etoposide (7) flunitrazepam (500 nM) (8) haloperidol (50 nM) (9) ivermectin (50 nM) (10) loperamide (2 pM) (11) morphine (2 pM) (12) ondansetron...

Saha N, Datta H, Sharma PL. (1991). Effects of morphine on memory interactions with naloxone, propranolol, and haloperidol. Pharmacology. 42(1) 10-14. 

Cyclo(His-D-Leu) acts as a hydrolytic catalyst. Cyclo(Leu-Gly) blocks the development of (1) physical dependence on morphine, (2) tolerance to the pharmacological effects of /3-endorphin, (3) tolerance to haloperidol-induced catalepsy and hypothermia, and (4) dopaminergic supersensitivity after chronic morphine administration. Cyclo(Tyr-Arg), a synthetic analogue of kyortorphin (an endogenous analgesic peptide), and its A-methyl tyrosine derivatives are more potent than kyotorphin in the mouse tail pressure test. ... 

Fukase, H. et al., Effects of morphine, naloxone, buprenorphine, butorphanol, haloperidol and imi-pramine on morphine withdrawal signs in cynomolgus monkeys, Psychopharmacology, 116, 396,1994. 

When the pharmacologic properties of two compounds are compared, one may prove to be more potent and efficacious than the other. For instance, as an analgesic, morphine is more potent and more efficacious than acetylsalicylic acid. On the other hand, two compounds may be equally efficacious but one could be more potent. Haloperidol and chlorpromazine are both efficacious neuroleptics in the management of schizophrenia, but haloperidol is more potent. 

Fig. 3.1 Morphine 1 has been the lead structure for the development of the major analgesic fentanyl 2, the antitussive drug dextromethorphan 3, the constipating drug loperamide 4, and the neuroleptic drug haloperidol 5.

De Ryck M, Schallert T, Teitelbaum P (1980) Morphine versus haloperidol catalepsy in the rat a behavioral analysis of postural support mechanisms. Brain Res 207 143-172. 

Figure 2.3 Dextromethorphan 6, the unnatural enantiomer of a narcotic morphine analog, is an antitussive drug. The antidiarrhea drug loperamide 7 and the neuroleptic drug haloperidol 8 also resulted from structural modification of morphine. The morphine antagonist nalorphine 9 differs from the opioid agonist morphine 3 (Figure 2.2) only by having an N-allyl group instead of the N-methyl group.

Paul Janssen s exploitation of 4-piperidone chemistry during the early 1960s proved remarkably successful in that it led to the clinical use of both a major tranquillizer (haloperidol)w and a potent narcotic analgesic, fentanyl.(2> Fentanyl (1, Sublimaze, Leptanol) is related to pethidine and also to basic anilides with analgesic properties such as diampromide 2 (p. 311) and is characterized by high potency and short duration of action. Thus, in mice (tail-clip method) fentanyl is almost 200 times as active as morphine by the sc route and has a faster onset and shorter duration of action than the standard... 

Drugs that are known to be substrates of P-gp include antihistamines (e.g. terfenadine), digoxin, ciclosporin, hydrocortisone and other steroids and drugs used in chemotherapy (e.g. paclitaxel, vinblastine). Ciclosporin, in addition to being a substrate of P-gp, is also an inhibitor of P-gp. Drugs known to induce P-gp include morphine, dexamethasone, phenobarbital, rifampin and St John s wort. Inhibitors of P-gp include amiodarone, amitriptyline, atorvastatin, chlorpromazine, ciclosporin, erythromycin, fluphenazine, haloperidol, quinidine, ritonavir and verapamil,... 

Antiemetics that act on the vomiting centre have antimuscarinic (their principal mode) and anti-histaminic action (hyoscine, promethazine) they alleviate vomiting from any cause. In contrast, drugs that act on the CTZ (haloperidol, ondansetron) are effective only for vomiting mediated by stimulation of the chemoreceptors (by morphine, digoxin, cytotoxics, uraemia). The most efficacious drugs act at more than one site (Table 31.1). 

Full agonists morphine, meperidine, methadone, fentanyl, and heroin Partial agonists buprenorphine, codeine, propoxyphene Mixed agonist-antagonists nalbuphine, pentazocine Antagonists naloxone, naltrexone Phenothiazines chlorpromazine, fluphenazine, thioridazine Others haloperidol, clozapine, risperidone, olanzapine... 

Presynaptic effect of morphine and haloperidol on dopamine synthesis Shyu, Bai-Chuang Chiang, Yi Wang, Wei-Kung... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, amitriptyline, amobarbital, amoxapine, antipsrrine, atenolol, atropine, azata-dine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bupivacaine, buspirone, butabarbital, butalbital, caffeine, carbamazepine, cetirizine, chlorqyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, qyclizine, (yclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, dipheno late, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fii-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydro g chloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, midazolam, moclobemide, morphine, nadolol, nalbuphine, naloxone, naphazoline, naproxen, nifedipine, nizatidine, norepinephrine, nortriptyline, oxazepam, oxycodone, oxymetazo-line, paroxetine, pemoline, pentazocine, pentobarbital, pentoxifylline, perphenazine, pheniramine, phenobarbital, phenol, phenolphthalein, phentolamine, phenylbutazone, phenyltoloxamine, phenytoin, pimozide, pindolol, piroxicam, pramoxine, prazepam, prazosin, probenecid, procainamide, procaine, prochlorperazine, procyclidine, promazine, promethazine, propafenone, propantheline, propiomazine, propofol, propranolol, protriptyline, quazepam, quinidine, quinine, racemethorphan, ranitidine, remoxipride, risperidone, salicylic acid, scopolamine, secobarbital, sertraline, sotalol, spironolactone, sulfinpyrazone, sulindac, temazepam, terbutaline, terfenadine, tetracaine, theophylline, thiethyl-perazine, thiopental, thioridazine, thiothixene, timolol, tocainide, tolbutamide, tolmetin, trazodone, triamterene, triazolam, trifluoperazine, triflupromazine, trimeprazine, trimethoprim, trimipramine, verapamil, warfarin, xylometazoline, yohimbine, zopiclone... 

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