Miller S

References (8)

Title : Endocannabinoid metabolism and transport as targets to regulate intraocular pressure - Miller_2020_Exp.Eye.Res__108266
Author(s) : Miller S , Daily L , Dharla V , Gertsch J , Malamas MS , Ojima I , Kaczocha M , Ogasawara D , Straiker A
Ref : Experimental Eye Research , :108266 , 2020
Abstract : Cannabinoids are part of an endogenous signaling system found throughout the body, including the eye. Hepler and Frank showed in the early 1970s that plant cannabinoids can lower intraocular pressure (IOP), an effect since shown to occur via cannabinoid CB1 and GPR18 receptors. Endocannabinoids are synthesized and metabolized enzymatically. Enzymes implicated in endocannabinoids breakdown include monoacylglycerol lipase (MAGL) and fatty acid amide hydrolase (FAAH), but also ABHD6, ABHD12, NAAA, and COX-2. Inhibition of MAGL activity raises levels of the endocannabinoid 2-arachidonoyl glycerol and substantially lowers IOP. Blocking other cannabinoid metabolizing enzymes or cannabinoid transporters may similarly contribute to lowering IOP and so serve as therapeutic targets for treating glaucoma. We have tested blockers for several cannabinoid-metabolizing enzymes and transporters (FABP5 and membrane reuptake) for their ability to alter ocular pressure in a murine model of IOP. Of FAAH, ABHD12, NAAA, and COX2, only FAAH was seen to play a role in regulation of IOP. Only the FAAH blocker URB597 lowered IOP, but in a temporally, diurnally, and sex-specific manner. We also tested two blockers of cannabinoid transport (SBFI-26 and WOBE437), finding that each lowered IOP in a CB1-dependent manner. Though we see a modest, limited role for FAAH, our results suggest that MAGL is the primary cannabinoid-metabolizing enzyme in regulating ocular pressure, thus pointing towards a role of 2-arachidonoyl glycerol. Interestingly, inhibition of cannabinoid transport mechanisms independent of hydrolysis may prove to be an alternative strategy to lower ocular pressure.
ESTHER : Miller_2020_Exp.Eye.Res__108266
PubMedSearch : Miller_2020_Exp.Eye.Res__108266
PubMedID: 32979397

Title : Synthesis and evaluation of potent and selective MGL inhibitors as a glaucoma treatment - Alapafuja_2019_Bioorg.Med.Chem_27_55
Author(s) : Alapafuja SO , Malamas MS , Shukla V , Zvonok A , Miller S , Daily L , Rajarshi G , Miyabe CY , Chandrashekhar H , Wood J , Tyukhtenko S , Straiker A , Makriyannis A
Ref : Bioorganic & Medicinal Chemistry , 27 :55 , 2019
Abstract : Monoacylglycerol lipase (MGL) inhibition provides a potential treatment approach to glaucoma through the regulation of ocular 2-arachidonoylglycerol (2-AG) levels and the activation of CB1 receptors. Herein, we report the discovery of new series of carbamates as highly potent and selective MGL inhibitors. The new inhibitors showed potent nanomolar inhibitory activity against recombinant human and purified rat MGL, were selective (>1000-fold) against serine hydrolases FAAH and ABHD6 and lacked any affinity for the cannabinoid receptors CB1 and CB2. Protein-based (1)H NMR experiments indicated that inhibitor 2 rapidly formed a covalent adduct with MGL with a residence time of about 6 h. This interconversion process "intrinsic reversibility" was exploited by modifications of the ligand's size (length and bulkiness) to generate analogs with "tunable' adduct residence time (tau). Inhibitor 2 was evaluated in a normotensive murine model for assessing intraocular pressure (IOP), which could lead to glaucoma, a major cause of blindness. Inhibitor 2 was found to decrease ocular pressure by -4.5 mmHg in a sustained manner for at least 12 h after a single ocular application, underscoring the potential for topically-administered MGL inhibitors as a novel therapeutic target for the treatment of glaucoma.
ESTHER : Alapafuja_2019_Bioorg.Med.Chem_27_55
PubMedSearch : Alapafuja_2019_Bioorg.Med.Chem_27_55
PubMedID: 30446439

Title : Effects of donepezil on cognitive performance after sleep deprivation - Dodds_2011_Hum.Psychopharmacol_26_578
Author(s) : Dodds CM , Bullmore ET , Henson RN , Christensen S , Miller S , Smith M , Dewit O , Lawrence P , Nathan PJ
Ref : Hum Psychopharmacol , 26 :578 , 2011
Abstract : OBJECTIVES: To identify tasks that were sensitive to a temporary decline in cognitive performance after sleep deprivation and to investigate the ability of the acetylcholinesterase inhibitor donepezil to reverse any sleep deprivation-induced impairment. METHODS: Thirty healthy volunteers were administered either a 5-mg daily dose of donepezil or placebo for 14-17 days, in a double-blind parallel group design, then underwent either 24 h sleep deprivation or a normal night of sleep in non-blinded crossover, and were subsequently tested on a battery of cognitive tasks designed to measure different components of memory and executive function. RESULTS: Sleep deprivation selectively impaired performance on several memory tasks whilst also impairing non-memory function on these tasks. Performance on other tasks was spared. Despite partially reversing the decline in subjective alertness associated with sleep deprivation, treatment with donepezil failed to significantly reverse the decline in cognitive performance on any of the tasks. CONCLUSIONS: The results demonstrate the sensitivity of certain tests, particularly those that measure memory function, to cognitive impairment after sleep deprivation. The inability of donepezil to reverse this performance decline suggests that the sleep deprivation model of cognitive impairment may not be suitable for detecting pro-cognitive effects of cholinergic augmentation.
ESTHER : Dodds_2011_Hum.Psychopharmacol_26_578
PubMedSearch : Dodds_2011_Hum.Psychopharmacol_26_578
PubMedID: 22161694

Title : Sitagliptin: a dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes - Miller_2006_Ann.Pharmacother_40_1336
Author(s) : Miller S , St Onge EL
Ref : Annals of Pharmacotherapy , 40 :1336 , 2006
Abstract : OBJECTIVE: To review the pharmacology, pharmacokinetics, safety, and efficacy of sitagliptin, a dipeptidyl peptidase IV (DPP-IV) inhibitor in the management of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966-February 2006) was conducted for English-language articles using the terms dipeptidyl peptidase IV inhibitor, incretin, MK-0431, and sitagliptin. Abstracts from the American Diabetes Association annual meetings in 2004 and 2005 were included as sources of data. STUDY SELECTION AND DATA EXTRACTION: Articles pertaining to the pharmacology of sitagliptin, its pharmacokinetics, safety and efficacy were reviewed. DATA SYNTHESIS: Sitagliptin is a potent, competitive, reversible inhibitor of the DPP-IV enzyme. It is eliminated renally, with a terminal half-life of 11.8-14.4 hours. In Phase II clinical trials, sitagliptin was found to be superior to placebo for the treatment of type 2 diabetes mellitus. Results of a small trial comparing sitagliptin with glipizide indicate that both treatments are comparable. The efficacy of sitagliptin has also been demonstrated when used as adjunctive therapy with metformin. Few adverse effects have been reported. Weight gain and hypoglycemia have not been seen with sitagliptin therapy.
CONCLUSIONS: Based on its unique mechanism of action, sitagliptin will provide practitioners with an additional tool in the treatment of diabetes. Review of the literature to date implies sitagliptin may be effective as monotherapy in type 2 diabetes. In addition, existing evidence supports the use of sitagliptin as adjunct therapy to sulfonylureas and metformin. Another advantage of sitagliptin use is that it appears to be free from the adverse effects of weight gain and hypoglycemia that are associated with currently available treatments.
ESTHER : Miller_2006_Ann.Pharmacother_40_1336
PubMedSearch : Miller_2006_Ann.Pharmacother_40_1336
PubMedID: 16868220

Title : Acetylcholinesterase Autoimmunity In Vitro -
Author(s) : Tang H , Hammond P , Ermilov L , Miller S , Brimijoin S
Ref : In: Structure and Function of Cholinesterases and Related Proteins - Proceedings of Sixth International Meeting on Cholinesterases , (Doctor, B.P., Taylor, P., Quinn, D.M., Rotundo, R.L., Gentry, M.K. Eds) Plenum Publishing Corp. :149 , 1998
PubMedID:

Title : Biohemical studies on muscarinic receptors in porcine atrium -
Author(s) : Schimerlik MI , Miller S , Peterson GL , Rosenbaum LC , Tota MR
Ref : Trends in Pharmacological Sciences , Suppl :2 , 1986
PubMedID:

Title : Ligand interactions with the solubilized porcine atrial muscarinic receptor - Herron_1982_Biochemistry_21_515
Author(s) : Herron GS , Miller S , Manley WL , Schimerlik MI
Ref : Biochemistry , 21 :515 , 1982
Abstract : Ligand interactions with porcine atrial muscarinic receptor solubilized in a mixed-detergent system (0.4% w/v digitonin and 0.08% w/v cholate) are described. The solubilized receptor interacts with ligands in a stereospecific manner, showing about the same affinity for local anesthetics and antagonists as was found for the membrane-bound protein [Schimerlik, M. I., & Searles, R. P. (1980) Biochemistry 19, 3407-3413]. Agonists appear to interact with a single class of noninteracting sites that correspond to the low-affinity agonist sites in the membrane-bound preparation. Kinetic studies of L-[3H]quinuclidinyl benzilate binding to the receptor indicated a two-step mechanism. The first step, in rapid preequilibrium (K = 5.7 x 10(-9) M), was followed by a slow conformational change (k1 = 4 x 10(-3) s-1; k-1 = 1.7 x 10(-4) s-1) in the receptor-ligand complex. The overall dissociation constant calculated from the association kinetics (2.3 x 10(-10) M) agreed well with the thermodynamic value for Kov (2.5 x 10(-10) M); however, direct determination of K-1 gave a value about 4-fold lower (4.0 x 10(-5) s-1) than predicted. Possible reasons for this discrepancy are discussed.
ESTHER : Herron_1982_Biochemistry_21_515
PubMedSearch : Herron_1982_Biochemistry_21_515
PubMedID: 7066304

Title : Epidemic malathion poisoning in Pakistan malaria workers - Baker_1978_Lancet_1_31
Author(s) : Baker EL, Jr. , Warren M , Zack M , Dobbin RD , Miles JW , Miller S , Alderman L , Teeters WR
Ref : Lancet , 1 :31 , 1978
Abstract : In 1976, epidemic organophosphate insecticide poisoning due to malathion occurred among 7500 field workers in the Pakistan malaria control programme. In July, the peak month of the epidemic, it is estimated that there were about 2800 cases. In field studies low red-cell cholinesterase activities were associated with the signs and symptoms of organophosphate insecticide intoxication. Toxicity was seen with 3 different formulations of the insecticide and was greatest with the products containing increased amounts of isomalathion, a toxic malathion degradation product. Poor work practices, which had developed when D.D.T. was the primary insecticide for malaria control, resulted in excessive skin contact with and percutaneous absorption of the pesticide. Airborne malathion concentrations were very low. Implementation of good work practices and proscription of use of the 2 pesticide formulations most contaminated with isomalathion halted the epidemic in September. An extensive training programme and surveillance system for pesticide toxicity preceded 1977 spraying operations.
ESTHER : Baker_1978_Lancet_1_31
PubMedSearch : Baker_1978_Lancet_1_31
PubMedID: 74508