Laurence R Meyerson - Academia.edu (original) (raw)
Papers by Laurence R Meyerson
Chemotherapy, 1993
A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was f... more A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was found to have antiviral activity against respiratory syncytial virus (RSV) in the 2-10 microM range in plaque reduction assays and cytopathic-effect-inhibition assays. The material was also virucidal. The 50% effective concentration (EC50) for virucidal activity was 28 microM. Experiments were done to determine the mode(s) of RSV inhibition by SP-303. Interferon was not induced. SP-303 did not inhibit attachment at antiviral concentrations. However, the EC50 for inhibition of virus penetration by SP-303 was 0.48 +/- 0.19 microM. These data suggest that abolition of RSV penetration into host cells is one mechanism whereby SP-303 inhibits RSV replication.
Pharmacology, Biochemistry and Behavior, Feb 1, 1983
The dopaminergic properties of metoclopramide and four of its metabolites were determined in a se... more The dopaminergic properties of metoclopramide and four of its metabolites were determined in a series of in vivo and in vitro tests. In vivo measures included changes in dopamine turnover, serum prolactin levels and antagonism of apomorphine-induced stereotyped behavior. In each of these tests the four metabolites were either completely inactive or significantly less potent than the parent compound. The potency of metoclopramide and its metabolites in in vitro dopamine/neuroleptic receptor models was compared to the potency of standard reference compounds. In vitro results indicate
Archives of General Psychiatry, Apr 1, 1990
ABSTRACT
Pharmacology, Biochemistry and Behavior, Feb 1, 1986
The potency ot structurally rigid analogues ofdopamme (DA) at st~latal dopamme receptms was evalu... more The potency ot structurally rigid analogues ofdopamme (DA) at st~latal dopamme receptms was evaluated in rats using three types of assessments [a) effectiveness m producing iot,monal and smthng behaviors by mtrastnata[ mjectums (b) mhlbmon ot {3Hl-splropendol binding and (c) stlmulaturn o[ adenylate cyclase activity The compounds included apomorphme (APO) and Its analogues, (R)-2,10,11tnhydroxyaporphme (R-THA) and (R)-2-hydroxy-10,11-methylenedloxyaporphme (MDO-APO), 2-ammo-6,7-dlhydroxyammotetrahne (ADTN) and its analogue, exo-2-ammo-6 7-&hydroxybenzonorbornene (exo-amme) (R)-THA produced no sieleoL,,py yet it was a potent inhibitor ol [3H]-spuopendol binding and adenylate cyclase activity MDO-APO was qmte active m reducing stereotyp3, and stimulating cyclase activity, but tt showed low potency m displacing [3H]-splropendol The cxo-amme and ADq N wine equally potent m enhancing rotation and sndfing intensity, however, the tormer was completely m,ltmve m biochemical assessments Except lol IRj-I HA, all DA analogues studmd elicited dopammom~meuc behavioral a~.t~vmes ot c~rchng and smiting Relationships between the actions ot these drugs m the behavioral and biochemical as,,essments ale discussed Rigid dopamme analogues Apomorphme Exo-2-ammo-6 7-d~hydroxy-benzonorbornene
![Research paper thumbnail of Unusual binding of [3H] MDL 72222 in guinea pig hippocampus](https://attachments.academia-assets.com/107488683/thumbnails/1.jpg)
](Drug Development Research, 1991
MDL 72222 labeled a non-homogeneous population of sites in guinea pig hippocampal membranes (Kd, ... more MDL 72222 labeled a non-homogeneous population of sites in guinea pig hippocampal membranes (Kd, = 1 nM; Kd2 = 60 nM). The binding was not sodium dependent. Competition studies with a variety of characterizing agents showed displacement of [3H] MDL 72222 binding by 5-HT uptake inhibitors. [3H] MDL 72222 binding was not effectively displaced by established 5-HT3 antagonists. MDL 72222, fluoxetine, fluvoxamine and citalopram competitively inhibited the uptake of [3H] 5-HT into guinea pig hippocampal synaptosomes with Ki values of I .97, 0.02, 0.023, 0.049 FM, respectively. The results demonstrate that [ , HI MDL 72222 labels a non-homogeneous population of sites in guinea pig brain, as well as inhibiting 5-HT uptake into synaptosomal preparations.
Life Sciences, 1989
The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was satu... more The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was saturable and corresponded to a single high-affinity state. Solubilization of the bovine hippocampal membranes with 10 mM CHAPS containing 200 mM NaCl, renders a preparation which binds [3H] 8-OH-DPAT with high-affinity (Kd = 1.9 nM) and is guanine nucleotide sensitive and ketanserin insensitive. 50% of [3H] 8-OH-DPAT binding activity is solubilized. The presence of GMP-P(NH)P promotes a low-affinity (Kd = 9.6 nM) state which is characteristic of receptors coupled to G-proteins. GMP-P(NH)P markedly accelerates the dissociation [3H] 8-OH-DPAT from solubilized membranes while having negligible effects on association. Thus, the agonist can activate the terniary complex rather than to promote its formation. 8-OH DPAT, WB 4101 and 5-carboxamidotryptamine dose responsively inhibit soluble [3H] 8-OH-DPAT binding with IC(50) values of 16.1, 15.6 and 1.3 nM, respectively. The CHAPS solubilized membrane preparation retains many of the [3H] 8-OH-DPAT binding characteristics of the membrane bound form.
Journal of Organic Chemistry, Mar 1, 1984
Page 1. J. Org. Chem. 1984, 49, 947-948 947 added and the reaction mixture was left at 0 "C ... more Page 1. J. Org. Chem. 1984, 49, 947-948 947 added and the reaction mixture was left at 0 "C for 12 h. The crystalline (+)-Ipc2BH was isolated, washed with EE (3 X 30 mL), and dried at 25 "C at 12 mmHg: 51.5 g, 72% yield. The ...
Biochemical Pharmacology, Mar 1, 1985
Rats were treated with electroconvulsive shock (ECS), desmethylimipramine (DMI), ECS plus DMI, or... more Rats were treated with electroconvulsive shock (ECS), desmethylimipramine (DMI), ECS plus DMI, or diazepam. In vitro analyses showed that chronic ECS produced an elevated density of recognition sites for [3H]imipramine (IMI) in platelet membranes, but had no effect on membrane preparations derived from cortical tissue. A similar elevation in receptor binding was seen exclusively in platelets after chronic ECS plus DMI, whereas no effect was observed with DMI alone. Equilibrium dissociation constant (KD) values for [3H]IMI were also increased in platelet membranes from rats given chronic ECS or ECS plus DMI treatment. Chronic ECS or DMI administration produced a decreased density of beta-adrenergic recognition sites in frontal cortex and cerebellum as assessed by [3H]dihydroalprenolol (DHA) binding. The combination of ECS plus DMI produced a similar decrease. In addition, chronic diazepam administration produced a down-regulation of the beta-adrenergic receptor only in the cerebellum. These data provide evidence for the differential regulation of brain and peripheral neurotransmitter recognition sites.
Biochemical Pharmacology, Jun 1, 1979
Biochemical Pharmacology, May 1, 1976
... Seroton n creatinine >ulfate and tyramin c hydr mhloride were purchased from ('albioch... more ... Seroton n creatinine >ulfate and tyramin c hydr mhloride were purchased from ('albiochcm, La ,lolla. C'alif. I ) Sal,olinol hydrobrornide. ... The ordinate intercept is t,; the abscis,a intercept is t ,. h , and the slope is -Ih,.. [4(rsl]. Salsulinul and its structural analog. ...
Life Sciences, Oct 1, 1982
Life Sciences, 1981
The haloperldol-lnduced actlvatlon of strlatal tyroslne hydroxylase (TH) is well establlshed, but... more The haloperldol-lnduced actlvatlon of strlatal tyroslne hydroxylase (TH) is well establlshed, but the form(s) of the enzyme involved wlth this response remain(s) obscure. Rats were decapltated one hour after elther haloperldol (1 mg/kg) or 30 mlnutes after apomorphlne (2 mg/kg) In the presence or absence of pyrogallol (250 mg/kg) pretreatment. Subcellular fractions were prepared from strlatal tissue, and L-DOPA formation was measured using reverse phase, palred-ion HPLC with electrochemical detection. The results ind~cate that the ~n VlVO admln~stratlon of haloperidol, but not apomorphlne, shifts t~'esu-s'u'6"cellular distrlbutlon of striatal TH actlvity. Thls shlft occurred from the cytosol fractlon (S 2) to the crude mltochondrlal fractlon (P2)" No shlft in TH actlvlty was observed wlth~n the crude synaptosomal fraction after either drug. It ~s suggested that the ability of haloperldol to ~ncrease dopamlnerg~c activity in vlvo is associated ~nth a sh~ft in strlatal TH activity dlstrlbutTon.
Peptides, May 1, 1986
The chromatographic behavior of biologically relevant peptides and proteins in the molecular weig... more The chromatographic behavior of biologically relevant peptides and proteins in the molecular weight range between 200 and 200,000 dalton units were studied on a size exclusion matrix column consisting of an aqueous compatible dihydroxyalkyl bonded silica support. The mechanism of separation appears to be dependent on hydrodynamic radius, hydrophobic and ionic interactions. Support for this contention is based on the chromatographic properties of these peptides and proteins at different mobile phase ionic strengths and pH, oxidation state of amino acid residues and total hydrophobicity of the peptide or protein. This column is also capable of separating native angiotensin-I from its iodinated congener. Recoveries of proteins and peptides from this column ranged between 70-100%. Unlike typical reverse phase separations, this modified silica chromatographic media allows for an alternative technique employing aqueous eluents for rapid separation/isolation and purification of peptides and proteins from natural or synthetic sources.
Pharmacology, Biochemistry and Behavior, Jun 1, 1980
Effect of antidepressant agents on fl-adrenergic receptor and neurotransmitter regulato~ systems.... more Effect of antidepressant agents on fl-adrenergic receptor and neurotransmitter regulato~ systems. PHARMAC. BIOCHEM. BEHAV. 12(6) 943-948, 1980.-The effects of established and several novel antidepressant agents on brain monoamine oxidase A and B; high affinity synaptosomal uptake of norepinephrine, dopamine and serotonin; and /3-adrenergic receptor kinetics evaluated by (3H)-dihydroalprenolol binding to cortical membranes are described. Extremely weak in vitro inhibitory effects on rat brain mitochondrial MAO-type A or B were observed with P74-1197 (+) or (-) and HP-505, both 3-aryl-spiroisobenzofuranpiperidines, P77-2984 a 3-aryl-spirobenzothiophenepiperidine derivative, LM-5008 an indolylethyipiperidine, desipramine, nisoxetine and P76-2543 a 4-aryl-l,3 benzodiazapine. As anticipated, deprenyl showed potent substrate selective inhibition of MAO type B. LM-5008, P74-1197(+) and P77-2984 were potent selective inhibitors of serotonin synaptosomal uptake while nisoxetine, P76-2543 and P74-1197(-) appeared to preferentially inhibit reuptake of norepinephrine. The kinetics (Bm,x and KD) of (3H)-dihydroalprenolol binding were also studied following chronic administration of these same drugs (10 mg/kg, b.i.d.). After 10 days of treatment, heterogeneous results were obtained in that some compounds elicited changes in receptor density and dissociation constant while others, such as nisoxetine, produced no kinetic alterations. While present biochemical antidepressant tests utilized in this study are designed to evaluate modulations of aminergic systems in terms of neurotransmitter availability, fluxes in concentration and attendant receptor recognition site sensitivities, the underlying mode(s) of action at the cellular level still require further clarification. fl-Adrenergic receptor Antidepressants Monoamine uptake inhibition Dihydroalprenolol binding Receptor sensitivity Monoamine oxidase
Life Sciences, 1988
The present study characterizes a serotonin (5-HT) binding site on human platelet membranes, usin... more The present study characterizes a serotonin (5-HT) binding site on human platelet membranes, using [3H]8-OH-DPAT as the radioligand. [3H]8-OH-DPAT binds specifically and saturably to a site on human platelet membranes with an average KD of 43 nM and Bmax of 1078 fmol/mg protein. Determinations of IC50 values for various serotonergic characterizing agents in platelets for displacement of [3H]8-OH-DPAT were performed. For example, 8-OH-DPAT 5HT1A had an IC50 of 117 nM; TFMPP 5HT1B (2.3 microM0 and PAPP 1A + 5HT2 (9 microM); ipsapirone 5HT1A (21.1 microM) and buspirone 5HT1A (greater than 100 microM); ketanserin 5HT2 (greater than 100 microM); 5-HT uptake inhibitors: paroxetine (13 nM); chlorimipramine (73 nM) and fluoxetine (653 nM). The pharmacological inhibitory profile of the platelet 8-OH-DPAT site is not consistent with profiles reported for brain. 8-OH-DPAT does not inhibit [3H]imipramine binding, however, it does inhibit [3H]5-HT uptake in human platelets near 5-HT's Km value (IC50 = 2-4 microM). These results suggest that the human platelet site labeled by [3H]8-OH-DPAT is pharmacologically different from the neuronal site and probably is a component of the 5-HT transporter.
Antiviral Research, Feb 1, 1993
SP-303, a naturally occurring polyphenolic polymer (average M.W. = 2100 Da), was tested in cotton... more SP-303, a naturally occurring polyphenolic polymer (average M.W. = 2100 Da), was tested in cotton rats (Sigmoden hispidus) for antiviral activity against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) viruses, and for acute toxicity. Significant reductions in pulmonary RSV titers, compared to pulmonary RSV titers in comparably treated control animals, were seen in cotton rats given 1-10 mg SP-303/kg/day intraperitoneally (i.p.) on days 1 through to 3, after experimental inoculation with RSV. The minimum efficacious dose of SP-303 against PIV3, when given i.p. for 3 days, was 3 mg/kg/day. Higher doses of SP-303 could not be given i.p., as doses > or = 30 mg/kg/day given once daily by this route for 3 or more consecutive days caused both significant weight loss and death in infected or uninfected animals. Although no toxicity was observed following oral administration of up to 270 mg of SP-303 daily for 3 days, this compound had variable antiviral activity when given by this route.
Pharmacology, Biochemistry and Behavior, Jul 1, 1982
Elsevier eBooks, 1983
ABSTRACT The employment of microwave irradiation prior to the determination of endogenous compoun... more ABSTRACT The employment of microwave irradiation prior to the determination of endogenous compounds in the central nervous system has become the method of choice in a number of cases. However, the accumulated reports have also indicated that careful consideration must be given to possible artifacts in the results obtained using this technique. The orientation of the animal head with respect to the irradiation as well as the instrumental spatial design of the wave guides may lead to distinctly different patterns of heat deposition. These may adversely affect the fraction of targeted enzyme activities which are deactivated and may even lead to a pressure-induced tissue spreading phenomenon. The rigid confinement of the animal necessary for reproducibility has also been considered as a source of immobilization stress. The fundamental effect of microwave irradiation, i.e., heating, has seemingly been ignored by most workers to date. Heating may directly lead to destruction or formation of investigated compounds. Heating may also alter the composition of the tissue in a manner which will significantly change the analytical recovery of the desired species in subsequent procedures. This latter consideration is the focus of the current report. The absolute per cent recovery for both serotonin and N -methyl-5-hydroxytryptamine was found to be higher in tissue homogenates which were heated than those treated normally.
Pharmacology, Biochemistry and Behavior, Nov 1, 1990
Acid glycoprotein (AGP) is an "acute phase protein" whose expression is altered in several human ... more Acid glycoprotein (AGP) is an "acute phase protein" whose expression is altered in several human pathologies. Using antiserum from New Zealand white rabbits, a radial immunodiffusion assay for measuring AGP levels in rat plasma was developed operating in the range of 50-2500 Ixg/ml with high specificity. Standard curves were constructed (precipitin ring diameter 2 vs. p.g/ml AGP) yielding highly linear plots (r= .98). The plasma concentration of AGP in spontaneously hypertensive (SHR) rats was double that of the normotensive Kyoto-Wistar (WKY) rats (208 ± 10 vs. 118 ± 5 wg/ml). AGP induction by turpentine resulted in a 14-and 26-fold increase in AGP levels in SHR and WKY rats, respectively. Induction of AGP by dexamethasone injection was examined in the SHR and WKY rat strains resulting in a 5-and 12-fold increase in AGP levels, respectively. AGP concentration in whole brain of rats was determined to be 12.7 ± 1.8 ~g/g. AGP concentrations in SHR and WKY liver were also determined to be 159 ± 3 and 148 ± 5 Ixg/g liver tissue. cq-Acid glycoprotein, AGP Immunoassay Stress response Endogenous serotonin uptake modulator Biological marker
Drug Development Research, 1984
Pharmacological and biochemical evidence supports the existence of a heterogeneous population of ... more Pharmacological and biochemical evidence supports the existence of a heterogeneous population of benzodiazepine (BDZ) receptors. One major tool which has been used to identify distinct receptor subtypes is a novel series of triazolopyridazines (TPZ) that recognize two subpopulations (types I and II) of BDZ binding sites. Earlier studies demonstrated that y-aminobutyric acid (GABA) enhanced specific BDZ binding and protected a fraction of BDZ binding sites against heat inactivation. GABAlBDZ interactions were further investigated by studying the properties of those BDZ binding sites that are thermostable in the presence of 1.0 mM GABA when cortical membrane fragments are heated at 60°C.
Chemotherapy, 1993
A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was f... more A natural-product polyphenolic polymer of molecular weight 2,100 daltons designated SP-303, was found to have antiviral activity against respiratory syncytial virus (RSV) in the 2-10 microM range in plaque reduction assays and cytopathic-effect-inhibition assays. The material was also virucidal. The 50% effective concentration (EC50) for virucidal activity was 28 microM. Experiments were done to determine the mode(s) of RSV inhibition by SP-303. Interferon was not induced. SP-303 did not inhibit attachment at antiviral concentrations. However, the EC50 for inhibition of virus penetration by SP-303 was 0.48 +/- 0.19 microM. These data suggest that abolition of RSV penetration into host cells is one mechanism whereby SP-303 inhibits RSV replication.
Pharmacology, Biochemistry and Behavior, Feb 1, 1983
The dopaminergic properties of metoclopramide and four of its metabolites were determined in a se... more The dopaminergic properties of metoclopramide and four of its metabolites were determined in a series of in vivo and in vitro tests. In vivo measures included changes in dopamine turnover, serum prolactin levels and antagonism of apomorphine-induced stereotyped behavior. In each of these tests the four metabolites were either completely inactive or significantly less potent than the parent compound. The potency of metoclopramide and its metabolites in in vitro dopamine/neuroleptic receptor models was compared to the potency of standard reference compounds. In vitro results indicate
Archives of General Psychiatry, Apr 1, 1990
ABSTRACT
Pharmacology, Biochemistry and Behavior, Feb 1, 1986
The potency ot structurally rigid analogues ofdopamme (DA) at st~latal dopamme receptms was evalu... more The potency ot structurally rigid analogues ofdopamme (DA) at st~latal dopamme receptms was evaluated in rats using three types of assessments [a) effectiveness m producing iot,monal and smthng behaviors by mtrastnata[ mjectums (b) mhlbmon ot {3Hl-splropendol binding and (c) stlmulaturn o[ adenylate cyclase activity The compounds included apomorphme (APO) and Its analogues, (R)-2,10,11tnhydroxyaporphme (R-THA) and (R)-2-hydroxy-10,11-methylenedloxyaporphme (MDO-APO), 2-ammo-6,7-dlhydroxyammotetrahne (ADTN) and its analogue, exo-2-ammo-6 7-&hydroxybenzonorbornene (exo-amme) (R)-THA produced no sieleoL,,py yet it was a potent inhibitor ol [3H]-spuopendol binding and adenylate cyclase activity MDO-APO was qmte active m reducing stereotyp3, and stimulating cyclase activity, but tt showed low potency m displacing [3H]-splropendol The cxo-amme and ADq N wine equally potent m enhancing rotation and sndfing intensity, however, the tormer was completely m,ltmve m biochemical assessments Except lol IRj-I HA, all DA analogues studmd elicited dopammom~meuc behavioral a~.t~vmes ot c~rchng and smiting Relationships between the actions ot these drugs m the behavioral and biochemical as,,essments ale discussed Rigid dopamme analogues Apomorphme Exo-2-ammo-6 7-d~hydroxy-benzonorbornene
Drug Development Research, 1991
MDL 72222 labeled a non-homogeneous population of sites in guinea pig hippocampal membranes (Kd, ... more MDL 72222 labeled a non-homogeneous population of sites in guinea pig hippocampal membranes (Kd, = 1 nM; Kd2 = 60 nM). The binding was not sodium dependent. Competition studies with a variety of characterizing agents showed displacement of [3H] MDL 72222 binding by 5-HT uptake inhibitors. [3H] MDL 72222 binding was not effectively displaced by established 5-HT3 antagonists. MDL 72222, fluoxetine, fluvoxamine and citalopram competitively inhibited the uptake of [3H] 5-HT into guinea pig hippocampal synaptosomes with Ki values of I .97, 0.02, 0.023, 0.049 FM, respectively. The results demonstrate that [ , HI MDL 72222 labels a non-homogeneous population of sites in guinea pig brain, as well as inhibiting 5-HT uptake into synaptosomal preparations.
Life Sciences, 1989
The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was satu... more The binding of [3H] 8-OH-DPAT to membrane-bound 5-HT1A receptors from bovine hippocampus was saturable and corresponded to a single high-affinity state. Solubilization of the bovine hippocampal membranes with 10 mM CHAPS containing 200 mM NaCl, renders a preparation which binds [3H] 8-OH-DPAT with high-affinity (Kd = 1.9 nM) and is guanine nucleotide sensitive and ketanserin insensitive. 50% of [3H] 8-OH-DPAT binding activity is solubilized. The presence of GMP-P(NH)P promotes a low-affinity (Kd = 9.6 nM) state which is characteristic of receptors coupled to G-proteins. GMP-P(NH)P markedly accelerates the dissociation [3H] 8-OH-DPAT from solubilized membranes while having negligible effects on association. Thus, the agonist can activate the terniary complex rather than to promote its formation. 8-OH DPAT, WB 4101 and 5-carboxamidotryptamine dose responsively inhibit soluble [3H] 8-OH-DPAT binding with IC(50) values of 16.1, 15.6 and 1.3 nM, respectively. The CHAPS solubilized membrane preparation retains many of the [3H] 8-OH-DPAT binding characteristics of the membrane bound form.
Journal of Organic Chemistry, Mar 1, 1984
Page 1. J. Org. Chem. 1984, 49, 947-948 947 added and the reaction mixture was left at 0 "C ... more Page 1. J. Org. Chem. 1984, 49, 947-948 947 added and the reaction mixture was left at 0 "C for 12 h. The crystalline (+)-Ipc2BH was isolated, washed with EE (3 X 30 mL), and dried at 25 "C at 12 mmHg: 51.5 g, 72% yield. The ...
Biochemical Pharmacology, Mar 1, 1985
Rats were treated with electroconvulsive shock (ECS), desmethylimipramine (DMI), ECS plus DMI, or... more Rats were treated with electroconvulsive shock (ECS), desmethylimipramine (DMI), ECS plus DMI, or diazepam. In vitro analyses showed that chronic ECS produced an elevated density of recognition sites for [3H]imipramine (IMI) in platelet membranes, but had no effect on membrane preparations derived from cortical tissue. A similar elevation in receptor binding was seen exclusively in platelets after chronic ECS plus DMI, whereas no effect was observed with DMI alone. Equilibrium dissociation constant (KD) values for [3H]IMI were also increased in platelet membranes from rats given chronic ECS or ECS plus DMI treatment. Chronic ECS or DMI administration produced a decreased density of beta-adrenergic recognition sites in frontal cortex and cerebellum as assessed by [3H]dihydroalprenolol (DHA) binding. The combination of ECS plus DMI produced a similar decrease. In addition, chronic diazepam administration produced a down-regulation of the beta-adrenergic receptor only in the cerebellum. These data provide evidence for the differential regulation of brain and peripheral neurotransmitter recognition sites.
Biochemical Pharmacology, Jun 1, 1979
Biochemical Pharmacology, May 1, 1976
... Seroton n creatinine >ulfate and tyramin c hydr mhloride were purchased from ('albioch... more ... Seroton n creatinine >ulfate and tyramin c hydr mhloride were purchased from ('albiochcm, La ,lolla. C'alif. I ) Sal,olinol hydrobrornide. ... The ordinate intercept is t,; the abscis,a intercept is t ,. h , and the slope is -Ih,.. [4(rsl]. Salsulinul and its structural analog. ...
Life Sciences, Oct 1, 1982
Life Sciences, 1981
The haloperldol-lnduced actlvatlon of strlatal tyroslne hydroxylase (TH) is well establlshed, but... more The haloperldol-lnduced actlvatlon of strlatal tyroslne hydroxylase (TH) is well establlshed, but the form(s) of the enzyme involved wlth this response remain(s) obscure. Rats were decapltated one hour after elther haloperldol (1 mg/kg) or 30 mlnutes after apomorphlne (2 mg/kg) In the presence or absence of pyrogallol (250 mg/kg) pretreatment. Subcellular fractions were prepared from strlatal tissue, and L-DOPA formation was measured using reverse phase, palred-ion HPLC with electrochemical detection. The results ind~cate that the ~n VlVO admln~stratlon of haloperidol, but not apomorphlne, shifts t~'esu-s'u'6"cellular distrlbutlon of striatal TH actlvity. Thls shlft occurred from the cytosol fractlon (S 2) to the crude mltochondrlal fractlon (P2)" No shlft in TH actlvlty was observed wlth~n the crude synaptosomal fraction after either drug. It ~s suggested that the ability of haloperldol to ~ncrease dopamlnerg~c activity in vlvo is associated ~nth a sh~ft in strlatal TH activity dlstrlbutTon.
Peptides, May 1, 1986
The chromatographic behavior of biologically relevant peptides and proteins in the molecular weig... more The chromatographic behavior of biologically relevant peptides and proteins in the molecular weight range between 200 and 200,000 dalton units were studied on a size exclusion matrix column consisting of an aqueous compatible dihydroxyalkyl bonded silica support. The mechanism of separation appears to be dependent on hydrodynamic radius, hydrophobic and ionic interactions. Support for this contention is based on the chromatographic properties of these peptides and proteins at different mobile phase ionic strengths and pH, oxidation state of amino acid residues and total hydrophobicity of the peptide or protein. This column is also capable of separating native angiotensin-I from its iodinated congener. Recoveries of proteins and peptides from this column ranged between 70-100%. Unlike typical reverse phase separations, this modified silica chromatographic media allows for an alternative technique employing aqueous eluents for rapid separation/isolation and purification of peptides and proteins from natural or synthetic sources.
Pharmacology, Biochemistry and Behavior, Jun 1, 1980
Effect of antidepressant agents on fl-adrenergic receptor and neurotransmitter regulato~ systems.... more Effect of antidepressant agents on fl-adrenergic receptor and neurotransmitter regulato~ systems. PHARMAC. BIOCHEM. BEHAV. 12(6) 943-948, 1980.-The effects of established and several novel antidepressant agents on brain monoamine oxidase A and B; high affinity synaptosomal uptake of norepinephrine, dopamine and serotonin; and /3-adrenergic receptor kinetics evaluated by (3H)-dihydroalprenolol binding to cortical membranes are described. Extremely weak in vitro inhibitory effects on rat brain mitochondrial MAO-type A or B were observed with P74-1197 (+) or (-) and HP-505, both 3-aryl-spiroisobenzofuranpiperidines, P77-2984 a 3-aryl-spirobenzothiophenepiperidine derivative, LM-5008 an indolylethyipiperidine, desipramine, nisoxetine and P76-2543 a 4-aryl-l,3 benzodiazapine. As anticipated, deprenyl showed potent substrate selective inhibition of MAO type B. LM-5008, P74-1197(+) and P77-2984 were potent selective inhibitors of serotonin synaptosomal uptake while nisoxetine, P76-2543 and P74-1197(-) appeared to preferentially inhibit reuptake of norepinephrine. The kinetics (Bm,x and KD) of (3H)-dihydroalprenolol binding were also studied following chronic administration of these same drugs (10 mg/kg, b.i.d.). After 10 days of treatment, heterogeneous results were obtained in that some compounds elicited changes in receptor density and dissociation constant while others, such as nisoxetine, produced no kinetic alterations. While present biochemical antidepressant tests utilized in this study are designed to evaluate modulations of aminergic systems in terms of neurotransmitter availability, fluxes in concentration and attendant receptor recognition site sensitivities, the underlying mode(s) of action at the cellular level still require further clarification. fl-Adrenergic receptor Antidepressants Monoamine uptake inhibition Dihydroalprenolol binding Receptor sensitivity Monoamine oxidase
Life Sciences, 1988
The present study characterizes a serotonin (5-HT) binding site on human platelet membranes, usin... more The present study characterizes a serotonin (5-HT) binding site on human platelet membranes, using [3H]8-OH-DPAT as the radioligand. [3H]8-OH-DPAT binds specifically and saturably to a site on human platelet membranes with an average KD of 43 nM and Bmax of 1078 fmol/mg protein. Determinations of IC50 values for various serotonergic characterizing agents in platelets for displacement of [3H]8-OH-DPAT were performed. For example, 8-OH-DPAT 5HT1A had an IC50 of 117 nM; TFMPP 5HT1B (2.3 microM0 and PAPP 1A + 5HT2 (9 microM); ipsapirone 5HT1A (21.1 microM) and buspirone 5HT1A (greater than 100 microM); ketanserin 5HT2 (greater than 100 microM); 5-HT uptake inhibitors: paroxetine (13 nM); chlorimipramine (73 nM) and fluoxetine (653 nM). The pharmacological inhibitory profile of the platelet 8-OH-DPAT site is not consistent with profiles reported for brain. 8-OH-DPAT does not inhibit [3H]imipramine binding, however, it does inhibit [3H]5-HT uptake in human platelets near 5-HT's Km value (IC50 = 2-4 microM). These results suggest that the human platelet site labeled by [3H]8-OH-DPAT is pharmacologically different from the neuronal site and probably is a component of the 5-HT transporter.
Antiviral Research, Feb 1, 1993
SP-303, a naturally occurring polyphenolic polymer (average M.W. = 2100 Da), was tested in cotton... more SP-303, a naturally occurring polyphenolic polymer (average M.W. = 2100 Da), was tested in cotton rats (Sigmoden hispidus) for antiviral activity against respiratory syncytial (RSV) and parainfluenza type 3 (PIV3) viruses, and for acute toxicity. Significant reductions in pulmonary RSV titers, compared to pulmonary RSV titers in comparably treated control animals, were seen in cotton rats given 1-10 mg SP-303/kg/day intraperitoneally (i.p.) on days 1 through to 3, after experimental inoculation with RSV. The minimum efficacious dose of SP-303 against PIV3, when given i.p. for 3 days, was 3 mg/kg/day. Higher doses of SP-303 could not be given i.p., as doses > or = 30 mg/kg/day given once daily by this route for 3 or more consecutive days caused both significant weight loss and death in infected or uninfected animals. Although no toxicity was observed following oral administration of up to 270 mg of SP-303 daily for 3 days, this compound had variable antiviral activity when given by this route.
Pharmacology, Biochemistry and Behavior, Jul 1, 1982
Elsevier eBooks, 1983
ABSTRACT The employment of microwave irradiation prior to the determination of endogenous compoun... more ABSTRACT The employment of microwave irradiation prior to the determination of endogenous compounds in the central nervous system has become the method of choice in a number of cases. However, the accumulated reports have also indicated that careful consideration must be given to possible artifacts in the results obtained using this technique. The orientation of the animal head with respect to the irradiation as well as the instrumental spatial design of the wave guides may lead to distinctly different patterns of heat deposition. These may adversely affect the fraction of targeted enzyme activities which are deactivated and may even lead to a pressure-induced tissue spreading phenomenon. The rigid confinement of the animal necessary for reproducibility has also been considered as a source of immobilization stress. The fundamental effect of microwave irradiation, i.e., heating, has seemingly been ignored by most workers to date. Heating may directly lead to destruction or formation of investigated compounds. Heating may also alter the composition of the tissue in a manner which will significantly change the analytical recovery of the desired species in subsequent procedures. This latter consideration is the focus of the current report. The absolute per cent recovery for both serotonin and N -methyl-5-hydroxytryptamine was found to be higher in tissue homogenates which were heated than those treated normally.
Pharmacology, Biochemistry and Behavior, Nov 1, 1990
Acid glycoprotein (AGP) is an "acute phase protein" whose expression is altered in several human ... more Acid glycoprotein (AGP) is an "acute phase protein" whose expression is altered in several human pathologies. Using antiserum from New Zealand white rabbits, a radial immunodiffusion assay for measuring AGP levels in rat plasma was developed operating in the range of 50-2500 Ixg/ml with high specificity. Standard curves were constructed (precipitin ring diameter 2 vs. p.g/ml AGP) yielding highly linear plots (r= .98). The plasma concentration of AGP in spontaneously hypertensive (SHR) rats was double that of the normotensive Kyoto-Wistar (WKY) rats (208 ± 10 vs. 118 ± 5 wg/ml). AGP induction by turpentine resulted in a 14-and 26-fold increase in AGP levels in SHR and WKY rats, respectively. Induction of AGP by dexamethasone injection was examined in the SHR and WKY rat strains resulting in a 5-and 12-fold increase in AGP levels, respectively. AGP concentration in whole brain of rats was determined to be 12.7 ± 1.8 ~g/g. AGP concentrations in SHR and WKY liver were also determined to be 159 ± 3 and 148 ± 5 Ixg/g liver tissue. cq-Acid glycoprotein, AGP Immunoassay Stress response Endogenous serotonin uptake modulator Biological marker
Drug Development Research, 1984
Pharmacological and biochemical evidence supports the existence of a heterogeneous population of ... more Pharmacological and biochemical evidence supports the existence of a heterogeneous population of benzodiazepine (BDZ) receptors. One major tool which has been used to identify distinct receptor subtypes is a novel series of triazolopyridazines (TPZ) that recognize two subpopulations (types I and II) of BDZ binding sites. Earlier studies demonstrated that y-aminobutyric acid (GABA) enhanced specific BDZ binding and protected a fraction of BDZ binding sites against heat inactivation. GABAlBDZ interactions were further investigated by studying the properties of those BDZ binding sites that are thermostable in the presence of 1.0 mM GABA when cortical membrane fragments are heated at 60°C.