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  Subjects -> PHARMACY AND PHARMACOLOGY (Total: 575 journals)
Showing 1 - 200 of 253 Journals sorted by number of followers
Nature Reviews Drug Discovery     Full-text available via subscription   (Followers: 332)
International Journal of Drug Policy     Hybrid Journal   (Followers: 254)
Journal of Clinical Oncology     Hybrid Journal   (Followers: 242)
Journal of Medicinal Chemistry     Hybrid Journal   (Followers: 157)
Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 155)
Drugs     Full-text available via subscription   (Followers: 146)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 98)
Pharmaceutical Research     Hybrid Journal   (Followers: 94)
European Journal of Pharmaceutical Sciences     Hybrid Journal   (Followers: 86)
Drug Safety     Full-text available via subscription   (Followers: 83)
Annals of Pharmacotherapy     Hybrid Journal   (Followers: 56)
Biomaterials     Hybrid Journal   (Followers: 54)
Clinical Pharmacology & Therapeutics     Hybrid Journal   (Followers: 44)
Regulatory Toxicology and Pharmacology     Hybrid Journal   (Followers: 42)
Journal of Controlled Release     Hybrid Journal   (Followers: 38)
Annual Review of Pharmacology and Toxicology     Full-text available via subscription   (Followers: 38)
International Journal of Pharmaceutics     Hybrid Journal   (Followers: 37)
Clinical Therapeutics     Hybrid Journal   (Followers: 34)
European Journal of Pharmaceutics and Biopharmaceutics     Hybrid Journal   (Followers: 34)
Pharmacoepidemiology and Drug Safety     Hybrid Journal   (Followers: 33)
British Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 32)
Journal of Pharmacy and Pharmacology     Full-text available via subscription   (Followers: 31)
Drug Development and Industrial Pharmacy     Hybrid Journal   (Followers: 29)
PharmacoEconomics     Full-text available via subscription   (Followers: 27)
Clinical Pharmacokinetics     Full-text available via subscription   (Followers: 27)
AAPS Journal     Hybrid Journal   (Followers: 26)
Critical Reviews in Toxicology     Hybrid Journal   (Followers: 25)
Journal of Clinical Psychopharmacology     Hybrid Journal   (Followers: 24)
International Journal of Pharmacy Practice     Full-text available via subscription   (Followers: 24)
Toxicology and Applied Pharmacology     Hybrid Journal   (Followers: 24)
Chemical Research in Toxicology     Hybrid Journal   (Followers: 22)
Journal of Pharmacokinetics and Pharmacodynamics     Hybrid Journal   (Followers: 22)
Journal of Pain & Palliative Care Pharmacotherapy     Hybrid Journal   (Followers: 21)
Trends in Pharmacological Sciences     Full-text available via subscription   (Followers: 20)
Journal of Applied Toxicology     Hybrid Journal   (Followers: 19)
Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 19)
Pharmaceutical Development and Technology     Hybrid Journal   (Followers: 19)
American Journal of Cardiovascular Drugs     Hybrid Journal   (Followers: 19)
Clinical Trials     Hybrid Journal   (Followers: 18)
Toxicology     Hybrid Journal   (Followers: 18)
Journal of Pharmaceutical and Biomedical Analysis     Hybrid Journal   (Followers: 18)
Clinical Toxicology     Hybrid Journal   (Followers: 18)
International Journal of Toxicology     Hybrid Journal   (Followers: 17)
Critical Reviews in Clinical Laboratory Sciences     Hybrid Journal   (Followers: 16)
Journal of Clinical Pharmacy and Therapeutics     Hybrid Journal   (Followers: 16)
Journal of Natural Products     Hybrid Journal   (Followers: 16)
Pharmaceutical Statistics     Hybrid Journal   (Followers: 15)
Toxicology Letters     Hybrid Journal   (Followers: 15)
Journal of Pharmacy Practice     Hybrid Journal   (Followers: 15)
Psychopharmacology     Hybrid Journal   (Followers: 15)
Basic & Clinical Pharmacology & Toxicology     Hybrid Journal   (Followers: 14)
Cardiovascular Drugs and Therapy     Hybrid Journal   (Followers: 14)
European Journal of Clinical Pharmacology     Hybrid Journal   (Followers: 14)
Current Medicinal Chemistry     Hybrid Journal   (Followers: 13)
American Journal of Therapeutics     Hybrid Journal   (Followers: 13)
Drug and Chemical Toxicology     Hybrid Journal   (Followers: 13)
Journal of the American Pharmacists Association     Full-text available via subscription   (Followers: 13)
Clinical Research and Regulatory Affairs     Hybrid Journal   (Followers: 12)
Seminars in Hematology     Hybrid Journal   (Followers: 12)
Drug Discovery Today: Technologies     Full-text available via subscription   (Followers: 12)
Current Pharmaceutical Design     Hybrid Journal   (Followers: 12)
Journal of Oncology Pharmacy Practice     Hybrid Journal   (Followers: 12)
Journal of Psychopharmacology     Hybrid Journal   (Followers: 11)
Biopharmaceutics and Drug Disposition     Hybrid Journal   (Followers: 11)
Toxicology in Vitro     Hybrid Journal   (Followers: 11)
Drug Development Research     Hybrid Journal   (Followers: 11)
Drug Metabolism and Disposition     Hybrid Journal   (Followers: 11)
Seminars in Oncology Nursing     Full-text available via subscription   (Followers: 10)
Biochemical Pharmacology     Hybrid Journal   (Followers: 10)
Journal of Separation Science     Hybrid Journal   (Followers: 10)
CNS Drugs     Full-text available via subscription   (Followers: 10)
Current Pharmaceutical Biotechnology     Hybrid Journal   (Followers: 10)
Journal of Medical Marketing     Hybrid Journal   (Followers: 10)
Drugs & Aging     Full-text available via subscription   (Followers: 10)
European Neuropsychopharmacology     Hybrid Journal   (Followers: 9)
Food Additives & Contaminants Part A     Hybrid Journal   (Followers: 9)
Journal of Pharmacology and Experimental Therapeutics     Hybrid Journal   (Followers: 9)
Environmental Toxicology and Pharmacology     Hybrid Journal   (Followers: 9)
Medicinal Chemistry     Hybrid Journal   (Followers: 9)
Biometrical Journal     Hybrid Journal   (Followers: 9)
Drugs & Therapy Perspectives     Full-text available via subscription   (Followers: 9)
Prescriber     Hybrid Journal   (Followers: 9)
ChemMedChem     Hybrid Journal   (Followers: 9)
Current Opinion in Pharmacology     Hybrid Journal   (Followers: 9)
European Journal of Pharmacology     Hybrid Journal   (Followers: 8)
Inhalation Toxicology     Hybrid Journal   (Followers: 8)
Antiviral Research     Hybrid Journal   (Followers: 8)
Drug Metabolism Reviews     Hybrid Journal   (Followers: 8)
Progress in Neuro-Psychopharmacology and Biological Psychiatry     Hybrid Journal   (Followers: 8)
Human & Experimental Toxicology     Hybrid Journal   (Followers: 8)
Drug Delivery     Open Access   (Followers: 8)
BioDrugs     Full-text available via subscription   (Followers: 8)
Frontiers in Drug Design & Discovery     Hybrid Journal   (Followers: 8)
Expert Review of Pharmacoeconomics & Outcomes Research     Full-text available via subscription   (Followers: 8)
Experimental and Clinical Psychopharmacology     Full-text available via subscription   (Followers: 7)
Toxicology Mechanisms and Methods     Hybrid Journal   (Followers: 7)
Journal of Pharmacological and Toxicological Methods     Hybrid Journal   (Followers: 7)
Clinical and Experimental Pharmacology and Physiology     Hybrid Journal   (Followers: 7)
Scandinavian Journal of Clinical and Laboratory Investigation     Hybrid Journal   (Followers: 7)
Epilepsy Research     Hybrid Journal   (Followers: 7)
Clinical Drug Investigation     Full-text available via subscription   (Followers: 7)
Journal of Veterinary Pharmacology and Therapeutics     Hybrid Journal   (Followers: 6)
Toxicology and Industrial Health     Hybrid Journal   (Followers: 6)
Skin Pharmacology and Physiology     Full-text available via subscription   (Followers: 6)
Journal of Cardiovascular Pharmacology     Hybrid Journal   (Followers: 6)
AAPS PharmSciTech     Hybrid Journal   (Followers: 6)
Current Drug Discovery Technologies     Hybrid Journal   (Followers: 6)
Current Drug Delivery     Hybrid Journal   (Followers: 6)
Current Therapeutic Research     Open Access   (Followers: 6)
Expert Review of Cardiovascular Therapy     Full-text available via subscription   (Followers: 6)
Neuropharmacology     Hybrid Journal   (Followers: 5)
Current Drug Metabolism     Hybrid Journal   (Followers: 5)
Fitoterapia     Hybrid Journal   (Followers: 5)
Expert Review of Molecular Diagnostics     Full-text available via subscription   (Followers: 5)
Expert Review of Anti-infective Therapy     Full-text available via subscription   (Followers: 5)
Anti-Infective Agents     Hybrid Journal   (Followers: 5)
Toxicon     Hybrid Journal   (Followers: 5)
Medicinal Research Reviews     Hybrid Journal   (Followers: 5)
Investigational New Drugs     Hybrid Journal   (Followers: 5)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry     Hybrid Journal   (Followers: 5)
Current Cancer Therapy Reviews     Hybrid Journal   (Followers: 5)
Reviews of Physiology, Biochemistry and Pharmacology     Hybrid Journal   (Followers: 4)
Planta Medica     Hybrid Journal   (Followers: 4)
Current Vascular Pharmacology     Hybrid Journal   (Followers: 4)
Pharmaceutical Medicine     Full-text available via subscription   (Followers: 4)
Journal of Child and Adolescent Psychopharmacology     Hybrid Journal   (Followers: 4)
CNS Drug Reviews     Open Access   (Followers: 4)
Inpharma Weekly     Full-text available via subscription   (Followers: 4)
Journal of Labelled Compounds and Radiopharmaceuticals     Hybrid Journal   (Followers: 4)
Immunopharmacology and Immunotoxicology     Hybrid Journal   (Followers: 4)
International Journal of Pharmaceutical and Healthcare Marketing     Hybrid Journal   (Followers: 4)
Inflammation Research     Hybrid Journal   (Followers: 4)
Cancer Chemotherapy and Pharmacology     Hybrid Journal   (Followers: 4)
International Journal of Neuropsychopharmacology     Open Access   (Followers: 3)
Pharmacology & Therapeutics     Hybrid Journal   (Followers: 3)
Physiology International     Full-text available via subscription   (Followers: 3)
Cardiovascular Therapeutics     Open Access   (Followers: 3)
ASSAY and Drug Development Technologies     Hybrid Journal   (Followers: 3)
Pharmacopsychiatry     Hybrid Journal   (Followers: 3)
Chemotherapy     Full-text available via subscription   (Followers: 3)
Therapeutic Drug Monitoring     Hybrid Journal   (Followers: 3)
Current Drug Therapy     Hybrid Journal   (Followers: 3)
Research in Social and Administrative Pharmacy     Hybrid Journal   (Followers: 3)
PharmacoEconomics & Outcomes News     Full-text available via subscription   (Followers: 3)
Journal of Aerosol Medicine and Pulmonary Drug Delivery     Hybrid Journal   (Followers: 3)
Journal of Ethnopharmacology     Hybrid Journal   (Followers: 3)
Drug Resistance Updates     Hybrid Journal   (Followers: 3)
Journal of Pain Management & Medicine     Open Access   (Followers: 3)
Journal of Infection and Chemotherapy     Hybrid Journal   (Followers: 3)
Journal of Cardiovascular Pharmacology and Therapeutics     Hybrid Journal   (Followers: 3)
Current Pharmacogenomics and Personalized Medicine     Hybrid Journal   (Followers: 3)
Acta Pharmacologica Sinica     Hybrid Journal   (Followers: 3)
Microbial Drug Resistance     Hybrid Journal   (Followers: 3)
Frontiers in Medicinal Chemistry     Hybrid Journal   (Followers: 3)
Human Psychopharmacology Clinical and Experimental     Hybrid Journal   (Followers: 3)
BMC Pharmacology     Open Access   (Followers: 2)
The Brown University Psychopharmacology Update     Hybrid Journal   (Followers: 2)
International Clinical Psychopharmacology     Hybrid Journal   (Followers: 2)
Canadian Journal of Physiology and Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Drug Targeting     Hybrid Journal   (Followers: 2)
Inflammopharmacology     Hybrid Journal   (Followers: 2)
Journal of Inflammation     Open Access   (Followers: 2)
Fundamental & Clinical Pharmacology     Hybrid Journal   (Followers: 2)
Behavioural Pharmacology     Hybrid Journal   (Followers: 2)
Vascular Pharmacology     Hybrid Journal   (Followers: 2)
Pulmonary Pharmacology & Therapeutics     Hybrid Journal   (Followers: 2)
Biomedicine & Pharmacotherapy     Full-text available via subscription   (Followers: 2)
Clinical Neuropharmacology     Hybrid Journal   (Followers: 2)
Drugs in R & D     Full-text available via subscription   (Followers: 2)
International Immunopharmacology     Hybrid Journal   (Followers: 2)
Pharmacology Biochemistry and Behavior     Hybrid Journal   (Followers: 2)
Letters in Drug Design & Discovery     Hybrid Journal   (Followers: 2)
Archiv der Pharmazie     Hybrid Journal   (Followers: 2)
Pharmacological Reviews     Hybrid Journal   (Followers: 2)
Molecular Pharmacology     Hybrid Journal   (Followers: 2)
Journal of Microencapsulation: Microcapsules, Liposomes, Nanoparticles, Microcells, Microspheres     Hybrid Journal   (Followers: 2)
Toxicological & Environmental Chemistry     Hybrid Journal   (Followers: 2)
Particulate Science and Technology: An International Journal     Hybrid Journal   (Followers: 1)
Pharmacological Research     Hybrid Journal   (Followers: 1)
Current Enzyme Inhibition     Hybrid Journal   (Followers: 1)
Journal of Neuroimmune Pharmacology     Hybrid Journal   (Followers: 1)
Current Pharmaceutical Analysis     Hybrid Journal   (Followers: 1)
Current Neuropharmacology     Hybrid Journal   (Followers: 1)
Pharmacogenetics and Genomics     Hybrid Journal   (Followers: 1)
Journal of Texture Studies     Hybrid Journal   (Followers: 1)
Pharmaceutical Biology     Open Access  
Journal of Liposome Research     Hybrid Journal  
Toxin Reviews     Hybrid Journal  
Kaohsiung Journal of Medical Sciences     Open Access  
Redox Report     Open Access  
Pharmacology     Full-text available via subscription  
Pharmaceutical Chemistry Journal     Hybrid Journal  
NeuroMolecular Medicine     Hybrid Journal  
Journal of Ocular Pharmacology and Therapeutics     Hybrid Journal  
Harm Reduction Journal     Open Access  
Current Nanoscience     Hybrid Journal  
Infectious Disorders - Drug Targets     Hybrid Journal  
Current Bioactive Compounds     Hybrid Journal  
Cancer Biotherapy & Radiopharmaceuticals     Hybrid Journal  
Autonomic & Autacoid Pharmacology     Hybrid Journal  

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Similar Journals
Journal Cover
Journal of Pharmacology and Experimental Therapeutics
Journal Prestige (SJR): 1.586
Citation Impact (citeScore): 4
Number of Followers: 9  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Online) 1521-0103
Published by ASPET Homepage  [4 journals]
  • Interactive Effects of {micro}-Opioid and Adrenergic-{alpha}2 Receptor
           Agonists in Rats: Pharmacological Investigation of the Primary Kratom
           Alkaloid Mitragynine and Its Metabolite 7-Hydroxymitragynine [Behavioral
           Pharmacology]

    • Free pre-print version: Loading...

      Authors: Obeng, S; Leon, F, Patel, A, Zuarth Gonzalez, J. D, Chaves Da Silva, L, Restrepo, L. F, Gamez-Jimenez, L. R, Ho, N. P, Guerrero Calvache, M. P, Pallares, V. L. C, Helmes, J. A, Shiomitsu, S. K, Soto, P. L, McCurdy, C. R, McMahon, L. R, Wilkerson, J. L, Hiranita, T.
      Pages: 182 - 198
      Abstract: The primary kratom alkaloid mitragynine is proposed to act through multiple mechanisms, including actions at µ-opioid receptors (MORs) and adrenergic-α2 receptors (Aα2Rs), as well as conversion in vivo to a MOR agonist metabolite (i.e., 7-hydroxymitragynine). Aα2R and MOR agonists can produce antinociceptive synergism. Here, contributions of both receptors to produce mitragynine-related effects were assessed by measuring receptor binding in cell membranes and, in rats, pharmacological behavioral effect antagonism studies. Mitragynine displayed binding affinity at both receptors, whereas 7-hydroxymitragynine only displayed MOR binding affinity. Compounds were tested for their capacity to decrease food-maintained responding and rectal temperature and to produce antinociception in a hotplate test. Prototypical MOR agonists and 7-hydroxymitragynine, but not mitragynine, produced antinociception. MOR agonist and 7-hydroxymitragynine rate-deceasing and antinociceptive effects were antagonized by the opioid antagonist naltrexone but not by the Aα2R antagonist yohimbine. Hypothermia only resulted from reference Aα2R agonists. The rate-deceasing and hypothermic effects of reference Aα2R agonists were antagonized by yohimbine but not naltrexone. Neither naltrexone nor yohimbine antagonized the rate-decreasing effects of mitragynine. Mitragynine and 7-hydroxymitragynine increased the potency of the antinociceptive effects of Aα2R but not MOR reference agonists. Only mitragynine produced hypothermic effects. Isobolographic analyses for the rate-decreasing effects of the reference Aα2R and MOR agonists were also conducted. These results suggest mitragynine and 7-hydroxymitragynine may produce antinociceptive synergism with Aα2R and MOR agonists. When combined with Aα2R agonists, mitragynine could also produce hypothermic synergism.SIGNIFICANCE STATEMENTMitragynine is proposed to target the µ-opioid receptor (MOR) and adrenergic-α2 receptor (Aα2R) and to produce behavioral effects through conversion to its MOR agonist metabolite 7-hydroxymitragynine. Isobolographic analyses indicated supra-additivity in some dose ratio combinations. This study suggests mitragynine and 7-hydroxymitragynine may produce antinociceptive synergism with Aα2R and MOR agonists. When combined with Aα2R agonists, mitragynine could also produce hypothermic synergism.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001192
      Issue No: Vol. 383, No. 3 (2022)
       
  • Self-Administration of Fentanyl-Alprazolam Combinations by Rhesus Monkeys
           Responding under a Progressive-Ratio Schedule [Behavioral Pharmacology]

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      Authors: Berro, L. F; Zamarripa, C. A, Rowlett, J. K.
      Pages: 199 - 207
      Abstract: This study evaluated the reinforcing effects of fentanyl, alone or in combination with the benzodiazepine alprazolam, in rhesus monkeys (3 females, 3 males). Subjects were trained to self-administer the opioid remifentanil (0.3 µg/kg/injection) under a progressive-ratio schedule of reinforcement. The reinforcing effects of fentanyl (0.1–10 µg/kg/injection) or alprazolam (1.0–100 µg/kg/injection) alone, or in combinations of fixed proportions (1:1, 1:3, and 3:1 fentanyl:alprazolam, with 1:1 based on the potencies of drugs alone) were evaluated in single-day test sessions (with double determinations). Dose-equivalence analysis was used to determine the extent to which fentanyl and alprazolam combinations differed from additivity. Fentanyl functioned as a positive reinforcer in all monkeys, while alprazolam was a reinforcer in 3 of 6 monkeys only. Therefore, drug combination data were grouped as "alprazolam-taking" and "non-alprazolam-taking" monkeys. For alprazolam-taking monkeys, we observed additive effects for the 3:1 and 1:3 combinations, and a significant supra-additive interaction for the 1:1 combination of fentanyl and alprazolam. For 2 of the 3 non-alprazolam-taking monkeys, the combination of fentanyl and alprazolam resulted in enhanced reinforcing effects relative to either drug alone. However, the one monkey showed primarily inhibitory, or suppressive effects, with the 3:1 dose combination resulting in a relatively modest rightward shift in the fentanyl dose-response function. In summary, our findings show that combining fentanyl and alprazolam generally result in proportion-dependent additive or supra-additive enhancements. These data raise the possibility that the prevalence of opioid-benzodiazepine polydrug abuse may reflect a unique enhancement of these drugs’ reinforcing effects, although individual differences may exist.SIGNIFICANCE STATEMENTAddressing the critical question of the degree to which benzodiazepines can modulate the abuse-related effects of opioids may provide improved pathways to treatment of this common form of polydrug addiction. In the present study, we show that combinations of the opioid fentanyl and the benzodiazepine alprazolam can be more reinforcing than either drug alone in a rhesus monkey model, suggesting that enhancement of reinforcement processes may underlie this prevalent form of polydrug use disorder.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001191
      Issue No: Vol. 383, No. 3 (2022)
       
  • Effects of a Novel Beta Lactam Compound, MC-100093, on the Expression of
           Glutamate Transporters/Receptors and Ethanol Drinking Behavior of
           Alcohol-Preferring Rats [Neuropharmacology]

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      Authors: Alhaddad, H; Wong, W, Abou-Gharbia, M, Childers, W, Melenski, E, Bell, R. L, Sari, Y.
      Pages: 208 - 216
      Abstract: Chronic ethanol exposure affects the glutamatergic system in several brain reward regions including the nucleus accumbens (NAc). Our laboratory has shown that chronic exposure to ethanol reduced the expression of glutamate transporter 1 (GLT-1) and cystine/glutamate exchanger (xCT) and, as a result, increased extracellular glutamate concentrations in the NAc of alcohol-preferring (P) rats. Moreover, previous studies from our laboratory reported that chronic ethanol intake altered the expression of certain metabotropic glutamate receptors in the brain. In addition to central effects, chronic ethanol consumption induced liver injury, which is associated with steatohepatitis. In the present study, we investigated the effects of chronic ethanol consumption in the brain and liver. Male P rats had access to a free choice of ethanol and water bottles for five weeks. Chronic ethanol consumption reduced GLT-1 and xCT expression in the NAc shell but not in the NAc core. Furthermore, chronic ethanol consumption increased fat droplet content as well as peroxisome proliferator-activated receptor alpha (PPAR-α) and GLT-1 expression in the liver. Importantly, treatment with the novel beta-lactam compound, MC-100093, reduced ethanol drinking behavior and normalized the levels of GLT-1 and xCT expression in the NAc shell as well as normalized GLT-1 and PPAR-α expression in the liver. In addition, MC-100093 attenuated ethanol-induced increases in fat droplet content in the liver. These findings suggest that MC-100093 may be a potential lead compound to attenuate ethanol-induced dysfunction in the glutamatergic system and liver injury.SIGNIFICANCE STATEMENTThis study identified a novel beta-lactam, MC-100093, that has demonstrated upregulatory effects on GLT-1. MC-100093 reduced ethanol drinking behavior and normalized levels of GLT-1 and xCT expression in the NAc shell as well as normalized GLT-1 and PPAR-α expression in the liver. In addition, MC-100093 attenuated ethanol-induced increases in fat droplet content in the liver.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001147
      Issue No: Vol. 383, No. 3 (2022)
       
  • A Physiologically-Based Pharmacokinetic Model of the Brain Considering
           Regional Lipid Variance [Neuropharmacology]

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      Authors: Heitman, A. M; Bies, R. R, Schwartz, S. L.
      Pages: 217 - 226
      Abstract: Modeling and simulation of the central nervous system provides a tool for understanding and predicting the distribution of small molecules throughout the brain tissue and cerebral spinal fluid (CSF), and these efforts often rely on empirical data to make predictions of distributions to move toward a better mechanistic understanding. A physiologically based pharmacokinetic model presented here incorporates multiple means of drug distribution to assemble a model for understanding potential factors that may determine the distribution of drugs across various regions of the brain, including both intra- and extracellular regions. Two classes of parameters are presented. The first concerns regional gross anatomic variability of the brain; the second concerns estimation of unbound fractions of drugs using know membrane phospholipid heterogeneity derived from regional lipid content. The model was then tested by comparing its outcomes to data from published human pharmacokinetic studies of acetaminophen, morphine, and phenytoin. The alignment of model predictions in the plasma, CSF, and tissue concentrations with the published data from studies of those three drugs suggests that the model can be a template for identifying drug localization in the brain. Clearly, knowledge of differentiated drug distribution in the brain is a requisite step in postulating pharmacodynamic and certain disease mechanisms.SIGNIFICANCE STATEMENTThis study concerns the application of heterogenous lipid distribution in brain tissue to predict regional variations in drug distribution in the brain via a mathematical model, thus expanding upon the current understanding of mechanisms of drug distribution in the central nervous system.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001256
      Issue No: Vol. 383, No. 3 (2022)
       
  • Botulinum Toxin A, a Better Choice for Skeletal Muscle Block in a
           Comparative Study With Lidocaine in Rats [Neuropharmacology]

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      Authors: Xu, K; Zhang, Z, Li, Y, Song, L, Gou, J, Sun, C, Li, J, Du, S, Cao, R, Cui, S.
      Pages: 227 - 237
      Abstract: A positive response to scalene muscle block (SMB) is an important indication for the diagnosis of thoracic outlet syndrome. Lidocaine injection is commonly used in clinical practice in SMB, although there have been some cases of misdiagnosis. Botulinum toxin A (BTX-A) is one of the therapeutic agents in SMB, but whether it is also indicated for SMB diagnosis is controversial. To evaluate the muscle block efficiency of these two drugs, the contraction strength was repeatedly recorded on tibialis anterior muscle in rats. It was found that at a safe dosage, 2% lidocaine performed best at 40 μL, but it still exhibits an unsatisfactory partial blocking efficiency. Moreover, neither lidocaine injection in combination with epinephrine or dexamethasone nor multiple locations injection could improve the blocking efficiency. On the other hand, injections of 3, 6, and 12 U/kg BTX-A all showed almost complete muscle block. Gait analysis showed that antagonistic gastrocnemius muscle, responsible for heel rising, was paralyzed for nonspecific blockage in the 12 U/kg BTX-A group, but not in the 3 U/kg or 6 U/kg BTX-A group. Cleaved synaptosomal associated protein 25 (c-SNAP 25) was stained to test the transportation of BTX-A, and was additionally observed in the peripheral muscles in 6 and 12 U/kg groups. c-SNAP 25, however, was barely detectable in the spinal cord after BTX-A administration. Therefore, our results suggest that low dosage of BTX-A may be a promising option for the diagnostic SMB of thoracic outlet syndrome.SIGNIFICANCE STATEMENTMuscle block is important for the diagnosis and treatment of thoracic outlet syndrome and commonly performed with lidocaine. However, misdiagnosis was observed sometimes. Here, we found that intramuscular injection of optimal dosage lidocaine only partially blocked the muscle contraction in rats, whereas low-dosage botulinum toxin, barely used in diagnostic block, showed almost complete block without affecting the central nervous system. This study suggests that botulinum toxin might be more suitable for muscle block than lidocaine in clinical practice.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001313
      Issue No: Vol. 383, No. 3 (2022)
       
  • Competitive Interactions Between Propofol and Diazepam: Studies in GABAA
           Receptors and Zebrafish [Neuropharmacology]

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      Authors: Pence, A; Hoyt, H, McGrath, M, Forman, S. A, Raines, D. E.
      Pages: 238 - 245
      Abstract: Although propofol is among the most commonly administered general anesthetics, its mechanism of action is not fully understood. It has been hypothesized that propofol acts via a similar mechanism as (R)-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (etomidate) by binding within the GABAA receptor transmembrane receptor domain at the two β+/α– subunit interfaces with resultant positive allosteric modulation. To test this hypothesis, we leveraged the ability of diazepam to bind to those sites and act as a competitive antagonist. We used oocyte-expressed α1β32L GABAA receptors to define the actions of diazepam (± flumazenil) on currents activated or potentiated by propofol and a zebrafish activity assay to define the impact of diazepam and flumazenil on propofol-induced anesthesia. We found that diazepam increased the amplitudes of GABAA receptor-mediated currents at nanomolar concentrations but reduced them at micromolar concentrations. The current amplitude changes produced by nanomolar diazepam concentrations were inhibited by flumazenil whereas those produced by micromolar diazepam concentrations were not. Studies of agonist potentiation showed that the micromolar inhibitory action of diazepam was surmountable by high concentrations of propofol and produced a rightward shift in the propofol concentration–response curve characterized by a Schild slope not statistically significantly different from 1, consistent with competition between diazepam and propofol. Although micromolar concentrations of diazepam (plus flumazenil) similarly reduced GABAA receptor currents modulated by propofol and etomidate, it only reduced the anesthetic actions of etomidate. We conclude that while both propofol and etomidate can modulate GABAA receptors by binding to the β+/α– subunit interfacial sites, propofol-induced anesthesia likely involves additional target sites.SIGNIFICANCE STATEMENTAlthough the drug combination of diazepam and flumazenil reverses the GABAA receptor positive modulatory actions of both propofol and (R)-ethyl 1-(1-phenylethyl)-1H-imidazole-5-carboxylate (etomidate), it only reverses the in vivo anesthetic actions of etomidate. These results strongly suggest that distinct mechanisms of action account for the anesthetic actions of these two commonly administered anesthetic agents.
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001337
      Issue No: Vol. 383, No. 3 (2022)
       
  • Comments on "Ocular Pharmacokinetics of Brimonidine Drug Delivery System
           in Monkeys and Translational Modeling for Selection of Dose and Frequency
           in Clinical Trials" [Letter to the Editor]

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      Authors: del Amo, E. M; Urtti, A, Ranta, V.-P.
      Pages: 246 - 247
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001257
      Issue No: Vol. 383, No. 3 (2022)
       
  • Response to Comments on "Ocular Pharmacokinetics of Brimonidine Drug
           Delivery System in Monkeys and Translational Modeling for Selection of
           Dose and Frequency in Clinical Trials" [Response Letter]

    • Free pre-print version: Loading...

      Authors: Tamhane, M; Luu, K. T, Attar, M.
      Pages: 248 - 249
      PubDate: 2022-11-11T10:01:10-08:00
      DOI: 10.1124/jpet.122.001439
      Issue No: Vol. 383, No. 3 (2022)
       
  • Correction to "Pharmacological Comparison of Mitragynine and
           7-Hydroxymitragynine: In Vitro Affinity and Efficacy for {mu}-Opioid
           Receptor and Opioid-Like Behavioral Effects in Rats" [Erratum]

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      Pages: 250 - 250
      PubDate: 2022-11-17T10:10:36-08:00
      DOI: 10.1124/jpet.120.000189err
      Issue No: Vol. 383, No. 3 (2022)
       
  • Correction to "Central Nervous System Delivery of the Catalytic Subunit of
           DNA-Dependent Protein Kinase Inhibitor Peposertib as Radiosensitizer for
           Brain Metastases" [Erratum]

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      Pages: 251 - 251
      PubDate: 2022-11-17T10:10:36-08:00
      DOI: 10.1124/jpet.121.001069err
      Issue No: Vol. 383, No. 3 (2022)
       
 
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