By I. Rune. Kennesaw State University.

According to its manufacturer buy combivent now, this antihis- tamine was not teratogenic in animal studies buy discount combivent 100 mcg on-line, although the study has not been published buy combivent australia. Triprolidine was not associated with an increased frequency of malformations in the offspring of 628 women who took this drug in the first trimester (Aselton et al. Ethanolamine/ethylamine derivatives Of 2847 infants exposed to clemastine during the first trimester, there was no increased frequency of congenital anomalies (Table 11. No human studies have been published regarding the use of bromodiphenhydramine and carbinoxamine, and neither have ani- mal teratology studies with either drug been published. The frequency of malformations was not increased in one animal study of carbinoxamine (Maruyama and Yoshida, 1968). In a large case–control study (23 757 cases; 39 877 controls), the risk of congenital anomalies was not increased among 2640 infants born to women who used dimenhy- drate during the first trimester (Czeizel and Vargha, 2005). Dimenhydrinate exposure during embryogenesis was not associated with an increased frequency of congenital anomalies in one animal study (McColl et al. Diphenhydramine was not associated with an increased frequency of congenital anomalies among 865 pregnancies exposed during the first trimester (Aselton et al. No studies regarding the use of bromodiphenhydramine during pregnancy have been published. Ten normal infants whose mothers were exposed to bromodiphenhydramine during gestation were included in the Collaborative Perinatal Project (Heinonen et al. Importantly, ethanolaminide derivatives have been reported to have oxytocic-like effects when used parenterally (Hara et al. Doxylamine was one of the main components of the popular antinausea drug, Bendectin (along with pyridoxine and dicyclomine). Some investigators reported an association of Bendectin use in pregnancy and diaphragmatic hernias (Bracken and Berg, 1983), congenital heart disease, and pyloric stenosis (Aselton et al. Other researchers found no such association with congenital anomalies fol- lowing exposure during embryogenesis (Mitchell et al. The frequency of congenital anomalies was not increased among more than 1100 infants exposed to doxylamine (an antihistamine component of Bendectin) Second-generation antihistamines 211 during the first trimester of pregnancy (Heinonen et al. No association was found between doxylamine and congenital heart disease in a case-controlled study (Zierler and Rothman, 1985), nor were malformations found to be increased in fre- quency in one animal teratology study of doxylamine (Gibson et al. Considering the millions of women who have used Bendectin during the first trimester of pregnancy without scientific evidence of adverse fetal effects, it is extremely unlikely that doxy- lamine or the components of Bendectin are human teratogens. Drugs such as Bendectin that do not cause birth defects, but are associated with lawsuits are called ‘litogens,’ i. Piperadine derivatives The frequency of congenital anomalies was not increased among 127 infants whose mothers took azatadine during the first trimester. Similarly, among 285 infants whose mothers took cyproheptadine during the first trimester, the frequency of congenital anomalies was not increased (see Table 11. There are no epidemiological studies of adverse fetal effects, including congenital malformations, in the offspring of mothers who took diphenylpyraline during pregnancy. Animal teratology studies of cyprohepta- dine are not consistent (de la Fuente and Alia, 1982; Rodriguez-Gonzalez et al. Ethylenediamine derivatives In a survey of 100 and 112 offspring exposed to tripelennamine and pyrilamine, respec- tively, during the first trimester, the frequency of congenital anomalies was not increased (Heinonen et al. Pyrilamine was associated with an increased rate of fetal loss in animal studies (Bovet-Nitti et al. Among 134 infants born to women who used terfenadine during the first trimester, there was no increased frequency of congen- ital anomalies (Schick et al. In a recent review, the frequency of congenital anom- alies among 2194 infants whose mothers took terfenadine during the first trimester was not increased (see Table 11. Terfenadine is not recommended for nursing mothers as it has been associated with decreased pup weight in rat studies (data from the manufacturer). Other second-generation antihistamines Among 950 infants whose mothers took cetirizine during the first trimester the fre- quency of congenital anomalies was not increased. Similarly, astemizole exposure dur- ing the first trimester was not associated with an increased frequency of congenital 212 Antihistamines, decongestants, and expectorants during pregnancy anomalies among 114 infants. These drugs seem safe for use during pregnancy, with greater confidence assigned to those drugs whose studies have the larger denominators (e. Piperazine derivatives Cyclizine, buclizine, and meclizine are used primarily as antiemetics, although they also have antihistamine action. Among over 1000 infants who were exposed to meclizine in the first trimester, the frequency of congenital anomalies was not increased (Heinonen et al. In addition, the risk of congenital anomalies was not increased by first- trimester exposure to meclizine in one cohort and three case–control studies (Greenberg et al. First-trimester exposure to cyclizine among 111 infants was not associated with an increased frequency of congenital anomalies (Milkovich and van den Berg, 1976). In a rat study, the frequency of craniofacial and skeletal malformations was increased among fetuses exposed to meclizine during embryogenesis (King, 1963). No birth defects were found in the offspring of monkeys who received 10 times the usual human dose of meclizine during embryogenesis (Courtney and Valerio, 1968; Wilson and Gavan, 1967). Phenindamine No animal or human studies regarding congenital anomalies and the use of phenin- damine in pregnant women have been published. However, it is closely related to chlor- pheniramine which has been studied during pregnancy and found not to increase the risk for birth defects (Table 11. Guaifenesin use dur- ing the first trimester in more than 1000 human pregnancies was not associated with an increased risk of congenital anomalies (Aselton, 1985; Heinonen et al. Other mucolytic agents or drugs that act as an expectorant include potassium iodide or iodinated glycerol. It is well known that iodine-containing agents cross the pla- centa freely and may result in fetal goiter. Therefore, iodide-containing agents are con- traindicated for use during pregnancy. It was used by 300 pregnant women during the first trimester and the frequency of congenital anomalies was not Expectorants and antitussives 213 Table 11. Numerous narcotics are used in cough preparations, including codeine, hydrocodone, and hydromorphone.

Reduction of this using hydrogen over Raney nickel cheap combivent 100mcg with amex, or action of aluminum amalgam buy combivent, or electrolytic reduction gives D best combivent 100mcg,L-epinephrine (11. Its action is very complex and depends not only on the relative distribution of adrenergic receptors in 11. The natural isomer of epinephrine ( ) is 50 times more active than the ( ) isomer. Activation of β1-adrenoreceptors increases the heart rate and strength of contractions of cardiac muscle. Activation of β2-adrenoreceptors leads to a dilation of bronchi and skeletal muscle blood vessels. Despite the fact that the primary pharma- cological action is reflected on the cardiovascular and respiratory systems, the complete spec- trum of its effects shows its physiological significance as a systemic neurohormone involved in the activation of a large number of protective functions. As a matter of fact, it is a prototype of many adrenergic drugs, and therefore its action on individual organ systems should be examined more carefully. A typical reaction upon intravenous introduction of epinephrine is the dramatic increase mainly in systolic blood pressure. A similar effect of epinephrine results from a combined action: first, contraction of the majority of blood vessels, and second, stimulation of the myocardium, which is expressed by the elevation of the strength of contractions and frequency of heartbeats. Epinephrine and other sympathomimetic drugs with β2-adreno-agonist properties are responsible for relaxation of bronchial muscles and an increase in bronchodilatation. Moreover, the α-adrenergic agonist activity of epinephrine is exhibited through the con- traction of pulmonary vessels and the development of antiedema effects. Epinephrine is used for relieving bronchial asthma, revival from anaphylactic shock, in hyperglycemic coma, and allergic reactions. It is used as a local vasoconstrictor, in partic- ular, in ophthalmology for reducing intraocular pressure. There is a large number of synonyms for epinephrine: adnephrine, adrenat, biorenin, epinal, hemostatin, nieralin, syndernin, and others. According to the first method, the indicated aldehyde is transformed into the cyanohydrin (11. This vasopressor catecholamine reduces both the resistance and capacity of blood vessels by stimulating α-adrenoreceptors and having a direct cardiostimulatory effect, which is accomplished by activation of β1-adrenoreceptors. Norepinephrine exhibits significantly less activity than epinephrine as a drug for widening blood vessels through the activation of β2-adrenoreceptors. Elevation of both stylistic and diastolic blood pressure is a typical reaction to intravenous introduction of norepinephrine. Norepinephrine is used for increasing cardiac constriction and for the necessary eleva- tion of blood pressure after sharp decline, which can result from surgical intervention or trauma. Interaction of ω-chloro-3,4- dihydroxyacetophenone (chloroacetylpyrocatechol) with isopropylamine gives ω-isopropy- lamino-3,4-dihydroxyacetophenone (11. As was already noted, the addition to compounds of a bulky iso-propyl or tert-butyl group at the nitrogen atom of the β-phenylethylamino skeleton is associated with higher affinity to β-adrenergic receptive regions than to α-adrenergic. Activation of β1-adrenergic receptors in the heart increases positive chronotropic and ionotropic action. Peripheral vascular resistance is increased by the widening of blood vessels, primarily in skeletal muscle, but also in renal and mesenteric blood circulation, which is caused by the β2-adrenergic system. In response to activation of β2-adrenorecep- tors, bronchodilation also increases. Synonyms of isoproterenol are proternol, isoprenaline, isadrine, norisodrine, novodrin, and others. However, it quickly calms bronchospasms better than more selective bronchodilators. Reduction of this product by hydrogen over a palladium catalyst leads to terbutaline (11. Adrenergic (Sympathomimetic) Drugs Terbutaline is a synthetic sympathomimetic amine. It stimulates smooth muscle β2-adrenoreceptors in the bronchi, relaxing them and relatively minutely acting on the β1—receptors of the heart. It is used for preventing and relieving bronchospasms in bronchial asthma, chronic bron- chitis, pulmonary emphysema, and other broncho-pulmonary diseases. A characteristic quality of phenylephrine is the distinctly expressed selectivity to α- adrenoreceptors, especially α1-adrenoreceptors. Although phenylephrine increases the contractibility of blood vessels, in practical terms it is not considered a cardiostimulant. Phenylephrine is used in hypotension, paroxysmal supraventricular tachycardia, and shock. It is also used locally, particularly in the form of nasal spray, for relieving edema. Synonyms of this drug are almefrine, degest, neoxedrin, metaoxedrin, and many others. The second major difference between the examined series is the replacement of the traditionally terminal iso-propyl or tert-butylamine region with a p-hydroxyphenylethy- lamine. Finally, the third difference is the presence of a methyl group at the α-atom of the phenylethylamine region of sympathomimetics, which makes it similar to isoetharine. This is reacted with 2-(4-benzy- loxyphenyl)ethylamine, forming an intermediate product (11. It is used as a tocolytic agent for problems associated with premature miscar- riages, and only in specialized medical facilities. According to the first, it is prepared from 4-hydroxyacetophe- none, the chloromethylation of which gives 4-hydroxy-3-hydroxymethylacetophenone (11. Reacting this with N-benzyl- N-tert-butylamine gives a derivative of aminoacetophenone (11. This is also reacted with N-benzyl-tert-buty- lamine, and the resulting product (11. It has expressed broncholytic effects—prevention or relief of bronchi spasms, lowering respiratory tract resistance, and increasing the vital capacity of the lungs. It is widely used for severe and chronic bronchial asthma and other illnesses of the res- piratory tract that result in a spastic condition of the bronchi. Synonyms of albuterol are aloprol, ventolin, volma, salbutamol, salbuvent, spreor, and others. Dobutamine: Dobutamine, ( ) 4-[2(4′-hydroxyphenyl)-1-methylpropyl]-3,4-dihydrox- yphenylethylamine (11. The second consider- able difference from the examined drugs is the presence of p-hydroxyphenyl-iso-buty- lamine group as a terminal amine substituent.

Individuals in treatment are often tested User accountability emphasizes that all users of to monitor their progress and provide them an illegal substances combivent 100 mcg low price, regardless of the type of drug incentive to remain drug free purchase genuine combivent line. It Treatment (therapeutic interventions) focus on is closely associated with zero tolerance order 100mcg combivent visa. The interventions may include medication, and users should be held fully accountable for their counseling, and other support services delivered in offenses under the law. These policies that focus only on some violators such as are demand reduction activities to eliminate or sellers of drugs or users of cocaine and heroin while reduce individuals’ drug use. Opium importation, domestic Problems with opiate addiction cultivation, manufacture, and trafficking limited/prohibited date from widespread use of (1887-1890) patent medicines in the 1800s. Pharmacy Act of 1868 The range of drugs included reguired registration of opium, morphine, laudanum, those dispensing drugs cocaine, and, by the turn of the century, heroin. The tonics, nostrums, and alleged cures that contained or used such drugs were sold by itinerant peddlers, mail order houses, retail grocers, and pharmacists. There also was unrestricted access to opium in opium-smoking dens and to morphine through retailers. When morphine was discovered Executive branch initiatives: in 1806, it was thought to be a wonder drug. Its use was so extensive during the Civil War that morphine addiction was termed the ‘‘army disease. After 1898, heroin was used to treat respiratory illness and morphine addiction in the belief that it was nonaddicting. Its use was supported first by activities; state and local dens (1875-90) the European medical community legislation and regulation and later by American medical authorities. In the absence of Cocaine introduced (mainly restrictive national legislation, its as a wine) as a lsubstitute for use spread. By 1900, in the face of an estimated quarter of a million addicts, State laws were enacted to curb drug addiction. The major 1860 1900 Major national drugs of abuse at the time were Civil War events cocaine and morphine. These Acts, intended dispensing of methadone stimulant drugs as a model for State legislation, generally have been adopted. Ongoing research may reclassify drugs from one category to another, as has happened in the past. The schedules shown below in simplified form are followed by extensive schedules (which are discussed fully in Volume 1, in the article entitled Controls: Scheduled Drugs/Drug Schedules, U. See also Alcohol 223–232 Abecarnil, 174 dehydrogenase; Aldehyde biopsychosocial model (See Abraxas Foundation, 1138 dehydrogenase Biopsychosocial model) Abscesses, from needles, 294 alcohol metabolism and, 74–75, 447–448 vs. See also craving and, 354–357 caffeine, 214 cultural considerations in (See Cultural drug interactions and, 438 Analgesics considerations) drug testing and, 450 with alcohol, 59, 60 defined, 23–24, 176, 314–315 nicotine, 785, 1201–1205 drug tampering and, 824 disease concept of (See Disease concept of Abstinence. See also Withdrawal liver toxicity and, 312 substance abuse) cirrhosis and, 311 propoxyphene with, 937 in elderly (See Elderly) cocaine triphasic model of, 224, 1254, Acetyl-CoA, 448 excessive behaviors, 822–823 1345–1346 Acetylation, 448 existential models of, 1307–1308 contingency management and, 1231 Acetylcholine, 16 genetics and (See Genetics) vs. See L-alpha-acetylmethadol myths about, 748–749 Abstinence violation effect, 1–2, 1165, 1229 Acetylsalicylic acid. See Aspirin neurotransmitters and, 777–800, 781 Abuse liability of drugs Acid (Slang). See Adult Children of Alcoholics psychological factors in (See Psychological 998–1000 Acquired immunodeficiency syndrome. See Alcohol, Drug Abuse and Public Health Service Hospitals and, 1305 hydromorphone, 618 Mental Health Administration Single Dose Questionnaire, 982 iatrogenic addiction and, 619–622 Addicted babies, 16–18. See Attention deficit/hyperactivity information regulation and, 685 barbiturates as, 160 disorder Partnership for a Drug-Free America and, for benzodiazepines, 174, 710 Adjective rating scales, 981–982 839–840 for catecholamine, 224 Adjunctive drug taking, 29–31 pharmaceutical industry and, 42–46 ibotenic acid as, 543 Administrative law, 31–33 tobacco industry and, 46–51, 47, 1098 for opioids, 986 Adolescents and substance abuse, 33, Advisory Council on the Misuse of Drugs partial (See Partial agonists) 33–36. See also specific types 602–607 African American Extended Family Program, of alcohol, e. See also Family violence cardiovascular disorders and (See rave parties, 951 alcohol and, 77, 87, 567–568, 654 Cardiovascular disorders, alcohol- religion and, 956–960, 957, 958, 959 anabolic steroids and, 125 related) smokeless tobacco, 1095, 1104–1105, animal research on, 978 child abuse and (See Child abuse) 1201 in children, 251–252 Chinese American use of, 254 state dependent learning and, 1001 club drugs and, 264 Chinese use of, 253 in Sweden, 1068 crime and, 53, 369–370 cholesterol and (See Cholesterol, alcohol Teen Addiction Severity Index, 20–21 alcohol-related, 360–361, 362–363 and) Toughlove and, 1110–1111 cocaine-related, 367 club drugs and, 264 vulnerability and opioids-related, 366 cocaethylene and, 75, 266–267 psychological factors, 353 driving drunk and, 470 cocarcinogenicity of, 219–220 sensation-seeking, 1326–1327 drugs and, 51–54, 523–524 complications from, 74–77, 462–463 sexual and physical abuse, 1327–1330 gangs, 566–567, 568 cardiovascular, 288–291, 321 Adolph Coors Co. See also Elderly muscular, 324 alcohol and, 295–296 Agonist-antagonists (Mixed), 63–64. See neurological, 331–334 opioids and, 297 also Receptors (Drug) nutritional, 323, 336–339 prednisone and, 1353 for opioids, 986 renal, 324 Adult Children of Alcoholics, 36–38, Agonists, 63, 1218–1219. See also respiratory, 322 176–177 Antagonists; Receptors (Drug) consumption per capita, 40–41 Adulteration of drug tests, 460–461 amantadine as, 106 creativity and, 358, 359 1824 Vol. See Wernicke-Korsakoff chlordiazepoxide as, 255 history of, 77–86 syndrome community-reinforcement approach, homelessness and, 613–618 Alcoholic cirrhosis. See Cirrhosis 1258–1259 imaging techniques and, 624 Alcoholic Control Act (Canada), 218 history of, 1123–1125 Italian use of, 670 Alcoholic dementia. See Dementia, alcohol- non-medical detoxification, 1246–1248 Jews and, 672–673 induced outpatient vs. See Liver enzymes sales, 41 antisocial personality disorder and, 138, Altered states of consciousness, 358, sensitizing agents (See Antidipsotropics) 327 587–588 temperance movement (See Temperance anxiety disorders and, 328–329 Amanita muscaria. See Fly agaric movement) benzodiazepines and, 177 Amantadine, 106, 1159, 1170–1171, 1254, treatment for abuse (See Alcoholism chronic, 102 1347 treatment) costs of, 42 Amazonian region, 266, 267 withdrawal from (See Alcohol withdrawal) craving theories of, 355 Ambien. See research and, 1276–1277 family violence and, 525–529 American Academy of Addiction Alcohol- and drug-free housing, 67–70, 585 genetics and, 36–37, 232–233, 1323 Psychiatry Alcohol abuse. See Phencyclidine Oriental Medicine, 1224 iatrogenic addiction and, 901 Angina pectoris, 1352 American Association of Advertising vs. See Peyote American Bar Association, 698, 1125 methamphetamine seizures, 117 Anhedonia, 112, 129, 224 American Board of Psychiatry and neurological complications from, 335 Anheuser-Busch Corp. See Amobarbital hallucinogens, 1024–1025 Harrison Narcotics Act of 1914 and, Anabolic steroids, 122–128, 123, 125 intracranial self-stimulation, 995–996 816–817 adolescents and, 35–36 learning factors, 996–1002 medical reforms and, 883–884 carcinogenicity of, 220 physical dependence and, 985–986 physician addiction and, 630 chemical structure of, 124 self-administration, 987–988, 993–994, treatment policy and, 1125 Anadrol. See Oxymetholone 1318–1319 on triplicate prescription, 1268 Analgesics, 128–129, 257, 829–832, 830. See Twelve step See American Psychiatric alcohol as, 336–337 programs Association buprenorphine as, 206, 828 Anorectic agents, 129 American Psychiatric Association. See also caffeine in, 210, 211 amphetamines as, 111, 385 Diagnostic and Statistical Manual cannabis as, 706 caffeine in, 210, 211 of Mental Disorders clonidine as, 263 iatrogenic addiction and, 901–902 on alcohol-related disorders, 399 comparison of, 831 Anorexia, 130 on benzodiazepines, 1019–1020 Dover’s powder, 416–417 Anslinger, Harry J. See Disulfiram American Psychological Association, 481 pain measurement and, 827–828 Antagonists, 134–135, 1219. See also American Public Health Association, 246 during pregnancy, 893–897 Agonists; Receptors (Drug) American Society of Addiction Medicine, stepwise treatment plan using, 257 for adenosine, 214–215 107–108, 933–934 Anaphylaxis for alcoholism, 1252 American Temperance Society, 1077, 1078 drug-induced, 105–106 as antidote, 136–137 American Temperance Union, 1360 immunoglobulin E and, 104–105 atropine as, 183 American Tobacco Company, 1093–1094 Anascha. See also specific for buprenorphine, 206–207 Aminergic neurotransmitters, 777–779 countries and regions, e. Greece, clonidine as, 262 Amino acid neurotransmitters, 777–779 ancient competitive (See Competitive antagonists) Aminorex, 1366 alcohol use in, 77–79, 164–165 for dopamine, 228 Amitriptyline, 439 betel nut use in, 183 flumazenil as, 941 Amnesia, alcohol-induced.

Use of rhodamine 123 to examine the functional activity of P-glycoprotein in primary cultured brain microvessel endo- thelial cell monolayers cheap combivent 100 mcg without a prescription. Functional expression of the P-glycoprotein mdr in primary cultures of bovine cerebral capillary endothelial cells discount combivent 100mcg otc. Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells buy genuine combivent online. Multidrug resistance-related trans- port proteins in isolated human brain microvessels and in cells cultured from these isolates. Transport of cyclosporin A across the brain capillary endothelial cell monolayer by P-glycoprotein. Restricted transport of cyclosporin A across the blood-brain barrier by a multidrug transporter, P-glycoprotein. Novel experimental parameters to quantify the mod- ulation of absorptive and secretory transport of compounds by P-glycoprotein in cell culture models of intestinal epithelium. Rhodamine 123 requires carrier-mediated influx for its activity as a P-glycoprotein substrate in Caco-2 cells. Development, validation and utility of an in vitro technique for assessment of potential clinical drug-drug interactions involving P-glycoprotein. In vitro p-glycoprotein inhibition assays for assessment of clinical drug interaction potential of new drug candidates: a recommendation for probe substrates. Retention of vital dyes correlates inversely with the multidrug-resistant phenotype of adriamycin-selected murine fibrosarcoma variants. Relationship between cytotoxic drug response patterns and activity of drug efflux transporters mediating multidrug resistance. Reciprocal correlation between expression of P-glycoprotein and accumulation of rhodamine 123 in human tumors. Rhodamine efflux patterns predict P-glycoprotein substrates in the National Cancer Institute drug screen. Transport of rhodamine 123, a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. Inhibitors of P-glycoprotein-mediated dauno- mycin transport in rat liver canalicular membrane vesicles. The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Role of P-glycoprotein as a secretory mechanism in quinidine absorption from rat small intestine. Effects of intestinal and hepatic metabolism on the bioavailability of tacrolimus in rats. Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine. Functional expression of mouse Mdr1 in an outer membrane permeability mutant of Escherichia coli. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Expression of human P-glycoprotein in yeast cells–effects of membrane component sterols on the activity of P-glyco- protein. Photometric microtiter assay of inorganic phos- phate in the presence of acid-labile organic phosphates. Human jejunal effective permeability and its correlation with pre- clinical drug absorption models. Hepatobiliary disposition of valproic acid and valproate glucuronide: use of a pharmacokinetic model to examine the rate-limiting steps and potential sites of drug interactions. Interactions between P-glycoprotein substrates and other cationic drugs at the hepatic excretory level. Hepatic sequestration and modulation of the canalicular transport of the organic cation, daunorubicin, in the Rat. Brain perfusion systems for studies of drug uptake and metabolism in the central nervous system. Kinetics of amino acid transport at the blood-brain barrier studied using an in situ brain perfusion technique. An in situ brain perfusion technique to study cerebrovascular transport in the rat. Facilitated transport of the neurotoxin, beta- N-methylamino-L-alanine, across the blood-brain barrier. Use of a physiologically based pharmacokinetic model to study the time to reach brain equilibrium: an experimental analysis of the role of blood-brain barrier permeability, plasma protein binding, and brain tissue binding. Development of a computational approach to predict blood-brain barrier permeability. Role of P-glycoprotein in the blood- brain transport of colchicine and vinblastine. New advances in the transport of doxorubicin through the blood-brain barrier by a peptide vector-mediated strategy. The effect of verapamil on the transport of peptides across the blood-brain barrier in rats: kinetic evidence for an apically polarized efflux mechanism. Regulation of protein secretion into bile: studies in mice with a disrupted mdr2 p-glycoprotein gene. Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease. The three mouse multidrug resistance (mdr) genes are expressed in a tissue-specific manner in normal mouse tissues. The gene encoding multidrug resistance is induced and expressed at high levels during pregnancy in the secretory epithelium of the uterus. Cloning and characterization of a member of the rat multidrug resistance (mdr) gene family. Differential overexpression of three mdr gene family members in multidrug-resistant J774.