Diazepam Scopolamine

A principle of the therapy for acute poisonings with OPC lies in the complex performance of cholinolytics (atropine, scopolamine, aprofene, amisile etc.) with reversible ChE inhibitors (pyridostigmine, proserine etc.) or cholinolytics with tranquillizers (diazepam, fenozepame etc)... 

Drug solutions and implantation of osmotic mini-pumps Physostigmine hemisulphate and procyclidine hydrochlorid were obtained from Sigma (St.Louis, U.S.A.), scopolamine hydrobromid from Merck (Darmstadt, Germany), atropine sulphate was obtained from ACF (Amsterdam, The Netherlands), and diazepam from Roche (The Netherlands). HI-6 was made available by the Defence Research Establishment, Suffield, Canada. Soman (O-pinacolyl methylphosphonofluoridate) was synthesised at TNO. Alzet Osmotic Mini-pumps with a constant delivery rate of 0.55 pl/hr (Model 2002, Alza Corp., Palo Alto, USA) were used to deliver PYR, PHY and SCO. The vehicle consisted of 20% propylene glycol, 10% ethanol and 70% water. The pumps were implanted subcutaneously under isoflurane/02 inhalation anesthesia. 

The NovaScan has received substantial testing in a number of laboratory and applied settings. Performance on the NovaScan has been demonstrated to be sensitive to the effects of alcohol, marijuana, diazepam, amphetamine, scopolamine, and an over-the-counter antihistamine.6 59 60 In addition, epidemiological differences in performance associated with gender, age, and occupation have been considered. Variations of the testing paradigm have been used in a number of commercial settings. 

GT-2016 also attenuated the PAR deficit induced by pretraining administration of either diazepam or scopolamine. Likewise, memory-enhancing properties were... 

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

Control Diaz Scopo Control Diaz Scopo Control Diaz Scopo I---------f Diazepam 5 mg/kg p.o. Scopolamine 0.5 mg/kg i.p. 

Fig. 14. Effects of diazepam and scopolamine on the 3 parameters measured during the acquisition of a delayed alternation task in the rat (mean performance over 10 sessions). Note that both diazepam and scopolamine significantly decrease the number of correct responses (impairment of learning/memory). Diazepam has no effect on simple reaction times whereas scopolamine significantly increases it (impairment of attention). Diazepam significantly decreases choice reaction times whereas choice reaction times are clearly increased by scopolamine. The increased choice reaction times with scopolamine probably reflect an impairment of information processing speed, whereas the decrease observed with diazepam probably reflects the disinhibitory effects of diazepam.

Ames, R., Steenland, K., Jenkins, B., Chrislop, D. and Russo, J. 1995. Chronic neurologic sequelae to cholinesterase inhibition among agriculture pesticide applicators. Arch. Environ. Health, 50 440-444. Anderson, D.R., Harris, L.W., Chang, F.-C.T., Baze, W.B., Capacio, B.R., Byers, S.L. and Lennox, W.J. 1997. Antagonism of soman-induced convulsion by midazolam, diazepam and scopolamine. Drug Chem. Toxicol, 20 115-131. 

The reactivators of ChE are ordinarily used with cholinolitics and anticonvulsant drugs like diazepam. We studied the pharmacokinetic of HI-6 administrated i.m. to rats alone, with Diazepam and Scopolamin and with them after soman intoxication [14],... 

HI-6 was administrated to rats in dose 36,0 mg/kg b.w. ( l,0xl0-4 M/kg b.w.), Diazepam - 2,5 mg/kg and Scopolamine - 0,5 mg/kg, b.w. administrated i.m. Rats intoxicated with 1,5 LD50 soman (70 pg/b.w., i.m.) were treated 1 min later with drug combination. A HPLC-method for analysis of HI-6 was used. Time-related plasma concentrations were fitted to one-compartment pharmacokinetic model. The result of plasma concentrations are presented in Figure 8 and pharmacokinetics parameters on Table 7. 

This studies are in agreement with our previous studies of HI-6 on cats. The combination of oxime with Scopolamine and Diazepame does not change its pharmacokinetic parameters. The concentration time profile of HI-6 after soman intoxication was shifted to the right. Further investigations have to be carried out with different doses of HI-6 and OPC in order to deepen our understanding of the changes in oxime pharmacokinetics after intoxication (14). 

Dishovsky, C., Ivanov, T., and Samnaliev, I., and Alexandrova, A., Pharmacokinetic of HI-6 combined with diazepam and scopolamine in rats, Toxicology Letters, 123,106,2001. 

Anderson DR, Harris LW, Chang F-C et al. (1997). Antagonism of soman-induced convulsions by midazolam, diazepam and scopolamine. Drug Chem Toxicol, 20, 115-131. 

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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