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1.
Pharmacogenomics J ; 13(6): 490-7, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23459442

ABSTRACT

The catechol-O-methyltransferase (COMT) Val158Met polymorphism may be a risk factor for nicotine addiction. This study examined the influence of the COMT Val158Met polymorphism on subjective, physiological and cognitive effects of intravenous (IV) nicotine use in African Americans (AAs; n=56) and European Americans (EAs; n=68) smokers. Overnight abstinent smokers received saline followed by 0.5 and 1.0 mg per 70 kg doses of nicotine, administered 30 min apart. Smokers with valine (Val)/Val genotype, compared with methionine (Met) carriers, had greater negative subjective effects from IV nicotine and had more severe withdrawal severity following overnight abstinence from smoking. Women with Val/Val genotype reported greater difficulty concentrating and irritability than men with Val/Val or Met carrier genotypes. The Val/Val genotype was associated with better performance on the math task and in AA smokers it was associated with greater systolic blood pressure. These results support the rationale of pharmacologically inhibiting COMT to aid with smoking cessation among Val/Val genotype smokers.


Subject(s)
Catechol O-Methyltransferase/genetics , Cognition/drug effects , Methionine/genetics , Nicotine/administration & dosage , Smoking , Substance Withdrawal Syndrome , Valine/genetics , Humans , Infusions, Intravenous , Nicotine/pharmacology
2.
Am J Drug Alcohol Abuse ; 26(1): 47-59, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10718163

ABSTRACT

We evaluated the effects of acute pretreatment with lamotrigine, a putative glutamate release inhibitor, on the physiological and behavioral responses to intranasal cocaine in cocaine-dependent volunteers (N = 8). The study employed a double-blind, placebo-controlled, within-subject design. Subjects participated in six experimental sessions. On each study day, placebo, lamotrigine 125 mg, or lamotrigine 250 mg was administered orally in the morning, followed 2 hours later by intranasal cocaine 120 mg/70 kg or placebo. Measurements of heart rate and blood pressure were acquired, and subjects responded to mood state questionnaires at predetermined time intervals. Cocaine alone produced increases in heart rate, blood pressure, and several measures of pleasurable mood and drug effects. Lamotrigine alone produced a mild relaxing effect. Lamotrigine pretreatment altered neither the physiological responses nor the subjective ratings of cocaine's pleasurable or aversive mood effects.


Subject(s)
Affect/drug effects , Arousal/drug effects , Blood Pressure/drug effects , Cocaine-Related Disorders/psychology , Excitatory Amino Acid Antagonists/pharmacology , Heart Rate/drug effects , Triazines/pharmacology , Administration, Oral , Adult , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Lamotrigine , Male , Premedication
3.
Am J Geriatr Psychiatry ; 6(3): 221-9, 1998.
Article in English | MEDLINE | ID: mdl-9659955

ABSTRACT

Low doses of neuroleptics are the standard for treating psychosis in elderly patients because of concern about inducing adverse effects. The authors found that fixed, low-dose neuroleptic treatment (0.15 mg/kg/day) for 10 days resulted in low perphenazine levels and low rates of acute response (25%) in elderly patients with primary psychotic illness (without dementia). Increase in initial dose did not speed acute response and induced adverse effects that were absent or minimal with low-dose treatment. With higher-dose treatment, drug blood levels rose disproportionately, and level-to-dose ratios were higher than those observed in non-elderly adults. Naturalistic follow-up suggested that response may take longer to develop than in non-elderly adults and that low doses for a longer duration may provide effective treatment.


Subject(s)
Antipsychotic Agents/pharmacology , Perphenazine/pharmacology , Psychotic Disorders/drug therapy , Aged , Aged, 80 and over , Antipsychotic Agents/blood , Antipsychotic Agents/therapeutic use , Chromatography, High Pressure Liquid , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance , Dyskinesia, Drug-Induced , Female , Follow-Up Studies , Geriatric Psychiatry/methods , Humans , Male , Perphenazine/blood , Perphenazine/therapeutic use , Treatment Outcome
4.
Biol Psychiatry ; 42(3): 181-90, 1997 Aug 01.
Article in English | MEDLINE | ID: mdl-9232210

ABSTRACT

This study evaluated the effect of an acute reduction in catecholamine synthesis produced by alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, on cocaine-induced euphoria. In a blinded, placebo-controlled study, AMPT (1 g p.o. T.I.D.) was given to 10 non-treatment-seeking cocaine abusers prior to intranasal administration of 2 mg/kg cocaine. AMPT, but not placebo, reduced plasma levels of the dopamine metabolite homovanillic acid and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol. AMPT also elevated prolactin levels, indicating inhibition of the tuberoinfundibular dopamine system. AMPT pretreatment produced a trend toward diminished cocaine "high" AMPT also tended to lower heart rate and blood pressure responses to cocaine, but had no effect on serum cocaine levels. Although we cannot rule out the therapeutic potential of the depletion strategy, our results with AMPT alone, at this dose, do not strongly support it.


Subject(s)
Cocaine , Enzyme Inhibitors/pharmacology , Euphoria/drug effects , Methyltyrosines/pharmacology , Substance-Related Disorders/physiopathology , Administration, Oral , Adult , Arousal/drug effects , Arousal/physiology , Diphenhydramine/pharmacology , Dopamine/physiology , Double-Blind Method , Euphoria/physiology , Female , Homovanillic Acid/blood , Humans , Male , Methoxyhydroxyphenylglycol/blood , Middle Aged , Norepinephrine/blood , Norepinephrine/physiology , Prolactin/blood , Substance-Related Disorders/psychology , alpha-Methyltyrosine
5.
Anesth Analg ; 84(1): 46-50, 1997 Jan.
Article in English | MEDLINE | ID: mdl-8988997

ABSTRACT

This study determined whether the development of delayed ischemic sequelae due to cocaine use--after the return of arterial blood pressure (BP) and heart rate to near-baseline values--may be attributable to regional vasoconstriction which persists beyond the acute systemic hemodynamic response. Five cocaine-using volunteers received intravenous infusions of saline placebo and cocaine 0.50 mg/kg several days apart in a double-blinded cross-over design. The intensity and duration of the cocaine-induced decrease in peripheral blood flow (as documented by laser Doppler flowmetry of the finger) were compared to the increases in BP (obtained with a Dinamap) and heart rate using paired t-test and repeated-measures analysis of variance. A significant increase in BP and a significant decrease in finger flow were noted by the first time point (5 min). Within 15 min, cocaine induced a 36% +/- 5% increase in BP and a 73% +/- 18% decline in finger flow (P < 0.05 for difference between percent change in BP and percent change in flow). Dinamap(systolic) and Dinamap(diastolic) returned to within 15% of baseline within 30 min, while finger flow remained more than 50% below baseline for the remainder of the 60-min study period (P < 0.05). Changes in heart rate paralleled those in BP. Except for isolated cases of documented coronary vasoconstriction in patients presenting with complications after cocaine use, this study is the first to document the persistence of cocaine-induced vasoconstriction of a sensitive vascular bed beyond the hypertensive response. It thus helps to explain the development of ischemic injury after cocaine use despite a stable rate-pressure product.


Subject(s)
Cocaine/adverse effects , Fingers/blood supply , Opioid-Related Disorders/physiopathology , Adult , Blood Pressure/drug effects , Cross-Over Studies , Depression, Chemical , Double-Blind Method , Heart Rate/drug effects , Humans , Ischemia/chemically induced , Laser-Doppler Flowmetry , Vasoconstriction/drug effects
6.
Brain Res ; 778(2): 418-29, 1997 Dec 19.
Article in English | MEDLINE | ID: mdl-9459563

ABSTRACT

Lewis and Fischer inbred rat strains differ in behavioral and biochemical responses to psychoactive drugs: Lewis rats show greater behavioral responses to psychoactive drugs than Fischer rats and they fail to show biochemical adaptations in the mesolimbic dopamine system after chronic drug exposure, in contrast to Fischer and outbred rats. This suggests that Fischer and Lewis rats may differ in the initial, reinforcing effects of psychoactive drugs, but not in responses seen after the exposure that occurs with maintenance of drug-reinforced behavior. Thus, the present study tested whether these strains differ in acquisition or maintenance of intravenous cocaine self-administration. Acquisition of cocaine self-administration was examined in separate groups that were allowed 15 days to acquire the operant at one of three cocaine doses (0.25, 0.5, or 1.0 mg/kg/infusion). Compared to Fischer rats, Lewis rats acquired cocaine self-administration after fewer training trials and at lower doses. After maintenance, both strains showed characteristic extinction responding with saline substitution and dose-related responding to cocaine, although Fischer rats tended to show higher response rates. Finally, cocaine plasma levels, obtained after an intravenous cocaine infusion (1.0 mg/kg), showed no strain differences suggesting that the strain difference in acquisition was not due to cocaine pharmacokinetics. These strain differences in acquisition of cocaine self-administration may be related to reported strain differences in the mesolimbic dopamine system. Further, because acquisition of drug self-administration is an animal model of vulnerability to drug addiction, these inbred strains may be useful to study factors underlying such vulnerability.


Subject(s)
Cocaine/pharmacokinetics , Dopamine Uptake Inhibitors/pharmacokinetics , Extinction, Psychological/drug effects , Rats, Inbred F344 , Rats, Inbred Lew , Animals , Behavior, Animal/drug effects , Cocaine/blood , Conditioning, Psychological/drug effects , Dopamine Uptake Inhibitors/blood , Injections, Intravenous , Life Tables , Male , Rats , Self Administration , Species Specificity , Substance-Related Disorders/physiopathology
7.
Brain Res ; 733(1): 133-7, 1996 Sep 09.
Article in English | MEDLINE | ID: mdl-8891259

ABSTRACT

The present study assessed the ability of cocaethylene to induce sensitization to the behavioral activating effects of cocaine in the male Sprague-Dawley rat. Preexposure to cocaethylene (15 or 25 mg/kg) significantly enhanced the locomotor activating effects of a subsequent cocaine (15 mg/kg) challenge injection. In addition, acute intraperitonecal administration at several doses (10, 15, or 25 mg/kg) confirmed previous reports of increased bioavailability of cocaine in brain and plasma relative to cocaethylene. These data are discussed in terms of previous work in which a significant augmentation of cocaine-induced locomotor activity was not observed following cocaethylene preexposure.


Subject(s)
Cocaine/analogs & derivatives , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Locomotion/drug effects , Analysis of Variance , Animals , Behavior, Animal/drug effects , Chromatography, High Pressure Liquid , Cocaine/blood , Cocaine/pharmacokinetics , Dopamine Uptake Inhibitors/blood , Dopamine Uptake Inhibitors/pharmacokinetics , Drug Interactions , Male , Neostriatum/chemistry , Rats , Rats, Sprague-Dawley , Sensitivity and Specificity
8.
J Pharmacol Exp Ther ; 274(1): 215-23, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7616402

ABSTRACT

Comorbid abuse of cocaine and alcohol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, is an active metabolite formed as a result of simultaneous use of these substances. In humans, the concurrent ingestion of cocaine and alcohol, with resulting cocaethylene formation, has been associated with enhanced subjective euphoria, increased heart rate and increased plasma cocaine concentration. These findings suggest that cocaethylene may play a role in the morbidity and mortality associated with concurrent cocaine/alcohol abuse. This placebo-controlled, double-blinded study examined the behavioral and physiological effects and pharmacokinetics of intranasal cocaethylene administration in humans (n = 8), using cocaine as a comparator. Cocaethylene administration resulted in a euphoria similar to that produced by cocaine, although the effects differed significantly over time. Subjects were unable to distinguish between equimolar doses of cocaine and cocaethylene, although cocaethylene appeared to be eliminated more slowly than cocaine. Cardiovascular effects of cocaethylene and cocaine were similar. These findings are considered in light of the epidemiology and possible consequences of cocaine and alcohol abuse.


Subject(s)
Behavior/drug effects , Blood Pressure/drug effects , Cocaine/analogs & derivatives , Dopamine Uptake Inhibitors/pharmacology , Heart Rate/drug effects , Cocaine/pharmacokinetics , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacokinetics , Double-Blind Method , Humans , Placebos
9.
Am J Clin Pathol ; 104(1): 82-8, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7611189

ABSTRACT

Pyrimethamine is an antiparasitic agent currently used for therapy of central nervous system toxoplasmosis, a disease seen with increasing frequency in association with the AIDS epidemic. Monitoring of pyrimethamine levels may be particularly important because patients may be treated with high doses of the drug for extended periods of time. The authors have developed and validated both a new enzyme inhibition assay that can be run on an automated analyzer and an improved high performance liquid chromatography (HPLC) method. The calibration range of both methods is 100 to 3,000 micrograms/L. Both demonstrate good linearity, specificity, and precision, and correlate well with one another (r = 0.99). The CVs of the enzyme inhibition assay were < or = 8.6% and those of the HPLC method were < or = 5.4%. No interference was noted for a variety of drugs likely to be used concomitantly with or in lieu of pyrimethamine with the exception of a minor interference from trimethoprim in the enzyme inhibition assay. The major advantage of the enzyme inhibition assay is its ease of automation. The major advantages of the HPLC assay are its precision and relative simplicity. These methods should facilitate therapeutic monitoring of pyrimethamine.


Subject(s)
Chromatography, High Pressure Liquid/standards , Clinical Enzyme Tests/standards , Enzyme Inhibitors/standards , Pyrimethamine/blood , Calibration , Chromatography, High Pressure Liquid/methods , Clinical Enzyme Tests/methods , Drug Monitoring , Folic Acid Antagonists , Humans , Linear Models , Pyrimethamine/pharmacology , Pyrimethamine/therapeutic use , Toxoplasmosis, Cerebral/drug therapy
10.
Psychopharmacology (Berl) ; 120(2): 150-5, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7480546

ABSTRACT

Cocaine and cocaethylene (a psychoactive metabolite of concurrent cocaine and ethanol consumption) were studied in the anesthetized vervet monkey. The ability of each to elevate extracellular DA in the caudate nucleus was assessed using microdialysis probes acutely lowered through chronic guide cannulae. Blood samples were also collected to determine plasma levels of the two drugs. Doses of 1.5 mumol/kg cocaine (equivalent to 0.5 mg/kg cocaine-HCl) and cocaethylene were administered intravenously. Microdialysis and blood samples were collected at 5-min intervals immediately following drug administration. Both drugs caused a maximal four-fold increase in extracellular DA during the 5- to 10-min period following drug administration. This is the first report of cocaine (and cocaethylene) induced alterations in extracellular DA in primates. The abilities of cocaine and cocaethylene to produce euphoria are being compared in ongoing clinical research studies. The potential use of these results for interpreting the neurochemical basis of any differences in those studies is discussed.


Subject(s)
Caudate Nucleus/drug effects , Cocaine/analogs & derivatives , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Dopamine/metabolism , Animals , Chlorocebus aethiops , Microdialysis , Time Factors
11.
J Clin Psychopharmacol ; 15(2): 99-105, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7782495

ABSTRACT

The authors investigated the relationship of desipramine concentrations in plasma to response, side effects, and dose in depressed patients over 75 years of age to determine if these "very old" patients were unusually sensitive to treatment. Thirty-four elderly patients consecutively hospitalized for nonpsychotic, unipolar major depression were treated with a fixed dose desipramine regimen for 4 weeks. Twelve nonresponding patients received a second trial at an increased dose. Comparisons were made with data from younger patients previously published by the authors. At comparable doses, steady-state desipramine concentrations in plasma in the elderly patients did not differ from those observed in younger patients. Response at levels in blood < 115 ng/ml was low, only 6 (21%) of 28 patient trials resulted in response. At levels > or = 115 ng/ml, 6 (46%) of 13 patient trials were effective. These rates were not significantly different. Inspection of the data revealed that a concentration in plasma of 105 ng/ml significantly separated responders and nonresponders (chi 2 = 3.93, df = 1, p < 0.05), but even at levels > or = 105 ng/ml, the response rate was still low relative to rates in prior studies of younger patients treated for a similar duration. The serious adverse reaction rate, 7 of 34, was similar to that previously observed in younger patients. This sample of "very old" elderly was not unusually "sensitive" to antidepressant drug treatment. In fact, the low rate of response observed at usually adequate levels in blood suggested "resistance" to treatment. The findings underscore the need for more effective drug treatments in the depressed elderly.


Subject(s)
Depressive Disorder/drug therapy , Desipramine/therapeutic use , Aged , Aged, 80 and over , Depressive Disorder/blood , Depressive Disorder/psychology , Desipramine/adverse effects , Desipramine/pharmacokinetics , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Humans , Male , Metabolic Clearance Rate , Patient Admission , Personality Inventory , Treatment Outcome
13.
Psychopharmacology (Berl) ; 116(3): 273-8, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7892416

ABSTRACT

Cocaethylene, a psychoactive metabolite resulting from combined ethanol/cocaine consumption, is of interest because its psychostimulant properties may partially underlie combined cocaine/ethanol use, and because it has the potential for use as a probe of drug reward mechanisms due to its enhanced selectivity at monoamine uptake sites compared to cocaine. To determine the relative systemic bioavailabilities of cocaine and cocaethylene, sequential plasma samples were obtained from awake rats following drug administration. Following intravenous administration of 3 mumol/kg (molar equivalent of 1 mg/kg cocaine-HCl), both drugs achieved similar time courses and areas under the plasma concentration versus time curve. In contrast, intraperitoneal administration of 44 mumol/kg (molar equivalent of 15 mg/kg cocaine HCl) showed peak plasma levels, and the area under the plasma concentration vs time curve for cocaine to be approximately twice that for cocaethylene. Comparison of dose corrected areas under the curve of the two routes of administration for each drug indicated that relative systemic bioavailability of cocaethylene following intraperitoneal administration is only 58% that of cocaine. In addition, the elimination of both cocaine and cocaethylene was found to be slower following intraperitoneal administration compared to the intravenous route. The implications of these results are discussed with respect to the relative potency of these two compounds, as inferred from behavioral, drug reward, and lethality studies. Also, the differences noted will need to be taken into account when making mechanistic interpretations from comparative drug reward studies.


Subject(s)
Cocaine/analogs & derivatives , Dopamine Uptake Inhibitors/pharmacokinetics , Reward , Animals , Biological Availability , Cocaine/blood , Cocaine/pharmacokinetics , Cocaine/pharmacology , Dopamine Uptake Inhibitors/blood , Dopamine Uptake Inhibitors/pharmacology , Injections, Intraperitoneal , Injections, Intravenous , Male , Rats , Rats, Sprague-Dawley
14.
Circulation ; 90(3): 1162-7, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7522132

ABSTRACT

BACKGROUND: Cocaine use has been associated with arterial occlusion resulting from platelet-rich thrombi and with an accelerated, often atypical atherosclerotic lesion that could be ascribed to platelet activation and platelet alpha-granule release. METHODS AND RESULTS: Using a flow cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha-granule membrane protein P-selectin), we found that 5 of 25 samples from 12 long-term cocaine users had a baseline level of circulating activated platelets > 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a significantly higher mean baseline level of circulating activated platelets (11.8 +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its metabolites, at concentrations documented as obtainable during in vivo cocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or aggregation, either directly or in concert with platelet agonists. However, in experiments in which cocaine users received blinded infusions of placebo or cocaine, the mean percent of circulating activated platelets rose significantly (P < .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65 +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging < 10(-6) mol/L. CONCLUSIONS: Long-term cocaine use in some subjects is intermittently associated with high basal levels of circulating platelets that have undergone alpha-granule release. The inability of cocaine and its metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P-selectin expression in vitro in this study, coupled with the acute increase in circulating activated platelets observed in vivo after either cocaine or placebo infusion, suggests that in vivo platelet alpha-granule release associated with cocaine use may occur through indirect rather than direct effects of the drug.


Subject(s)
Blood Platelets/drug effects , Cell Degranulation/drug effects , Cocaine/pharmacology , Cell Adhesion Molecules/blood , Cocaine/metabolism , Humans , P-Selectin , Pilot Projects , Platelet Activation/drug effects , Platelet Aggregation/drug effects , Platelet Membrane Glycoproteins/blood , Reference Values
15.
Clin Chem ; 40(2): 211-5, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8313596

ABSTRACT

Of the antiviral agents that are currently in clinical use in the US for therapy for human immunodeficiency virus infections, zalcitabine (ddC) is the most potent and is effective at the lowest plasma concentrations. The two reported procedures for measuring these low concentrations involve a chromatographic technique coupled with mass spectrometry. We have developed a procedure combining solid-phase extraction with a strong cation-exchange resin and commercially available RIA reagents for the quantification of ddC in plasma or serum. The method demonstrates good linearity, specificity, and precision, with overall CVs of < 10% from 2-20 micrograms/L and 17% at 0.8 microgram/L (the lower limit of quantitation). No significant cross-reactivity with nucleoside analogs other than ddC analogs was noted. The major advantages of this assay are its efficiency and relative simplicity, which should facilitate its performance in many laboratories.


Subject(s)
Antiviral Agents/blood , Radioimmunoassay , Zalcitabine/blood , Biological Availability , Half-Life , Humans , Male , Quality Control , Radioimmunoassay/statistics & numerical data , Sensitivity and Specificity , Zalcitabine/pharmacokinetics , Zidovudine/blood
16.
J Clin Psychiatry ; 55(1): 12-9, 1994 Jan.
Article in English | MEDLINE | ID: mdl-8294386

ABSTRACT

BACKGROUND: To determine the predictors of desipramine-refractory depression, the authors examined the outcome in patients with major depression who were admitted to a general hospital and treated with desipramine adjusted to an adequate blood level. METHOD: Sixty-eight consecutive inpatients with DSM-III nonpsychotic unipolar major depression who had failed to respond to 1 week of hospitalization without drug treatment were studied. Outcome was assessed with the Yale Depression Inventory after a 4-week desipramine trial in which 24-hour plasma concentrations were used to rapidly achieve a therapeutic desipramine level. RESULTS: Poor response to a therapeutic desipramine trial, which occurred in 15 of 50 patients, was significantly associated with definite personality disorder, prior treatment failure, near delusional status, age < or = 35 years, duration of depressive episode, recurrence of depression, dysthymia, and secondary depression. The first four items remained significantly correlated with poor response when the presence of the other items was accounted for using multiple regression. Drug response was not predicted by the diagnosis of melancholia (DSM-III and DSM-III-R) or initial severity of the depressive episode. CONCLUSION: The four strongest correlates of outcome were highly predictive of drug response. In patients with two or more predictors, only 25% (4 of 16) responded, while in those with one or no predictors, 91% (31 of 34) responded.


Subject(s)
Depressive Disorder/drug therapy , Desipramine/therapeutic use , Adult , Depressive Disorder/diagnosis , Depressive Disorder/psychology , Desipramine/administration & dosage , Desipramine/blood , Drug Administration Schedule , Female , Hospitalization , Humans , Male , Middle Aged , Probability , Psychiatric Status Rating Scales , Regression Analysis , Severity of Illness Index , Treatment Outcome
17.
Psychopharmacology (Berl) ; 111(1): 39-46, 1993.
Article in English | MEDLINE | ID: mdl-7870932

ABSTRACT

Simultaneous abuse of cocaine and ethanol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, has been detected in the urine of patients reporting concurrent use of cocaine and ethanol, and high levels have been found in the blood of victims of fatal drug overdose. This placebo-controlled, double-blind study examined the pharmacokinetic, physiologic, and behavioral effects of dual cocaine and ethanol administration in humans (n = 6). Cocaethylene was found in the plasma only after administration of both cocaine and ethanol, and appeared to be eliminated more slowly than cocaine. Plasma cocaine concentrations were significantly higher during cocaine/ethanol administration. Euphorigenic effects were both enhanced and prolonged, and heart rate was significantly increased, following cocaine/ethanol administration as compared to administration of cocaine or ethanol alone.


Subject(s)
Behavior/drug effects , Cocaine/analogs & derivatives , Dopamine Uptake Inhibitors/blood , Ethanol/pharmacology , Adult , Affect/drug effects , Blood Pressure/drug effects , Cocaine/blood , Cocaine/pharmacology , Double-Blind Method , Drug Interactions , Ethanol/blood , Euphoria/drug effects , Half-Life , Heart Rate/drug effects , Humans , Male
18.
Biol Psychiatry ; 32(12): 1102-7, 1992 Dec 15.
Article in English | MEDLINE | ID: mdl-1477190

ABSTRACT

The addition of lithium to perphenazine altered the pattern of plasma homovanillic acid (HVA) during the course of treatment for acute psychosis. In the perphenazine-treated group plasma HVA declined significantly by days 7-9 of treatment, whereas in the perphenazine-plus-lithium group plasma HVA tended to increase. The pattern for plasma methoxyhydroxyphenethyl-glycol (MHPG) was not significantly different for the two groups. The addition of lithium to a neuroleptic may enhance the metabolism of dopamine.


Subject(s)
Bipolar Disorder/drug therapy , Homovanillic Acid/blood , Lithium/administration & dosage , Methoxyhydroxyphenylglycol/blood , Perphenazine/administration & dosage , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Aged , Bipolar Disorder/blood , Bipolar Disorder/psychology , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Psychotic Disorders/blood , Psychotic Disorders/psychology , Schizophrenia/blood
19.
Psychiatry Res ; 41(2): 147-54, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1574541

ABSTRACT

Identification of symptoms that are directly responsive to neuroleptic drugs at progressive phases of treatment is important for monitoring drug response and understanding the relationship between neurochemical mechanisms of drug action and disordered behavior. Using multiple regression analyses that controlled for pretreatment severity, we identified those symptoms that improved in direct relation to serum concentrations of perphenazine after 10 days of treatment. Improvement in two positive symptoms of psychosis--hallucinations and conceptual disorganization--appears to be related to perphenazine level and useful for assessment of early drug response.


Subject(s)
Bipolar Disorder/drug therapy , Depressive Disorder/drug therapy , Perphenazine/therapeutic use , Psychiatric Status Rating Scales , Psychotic Disorders/drug therapy , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Benztropine/adverse effects , Benztropine/therapeutic use , Bipolar Disorder/blood , Bipolar Disorder/psychology , Depressive Disorder/blood , Depressive Disorder/psychology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Female , Haloperidol/adverse effects , Haloperidol/therapeutic use , Humans , Male , Perphenazine/adverse effects , Perphenazine/pharmacokinetics , Psychotic Disorders/blood , Psychotic Disorders/psychology , Schizophrenia/blood , Schizophrenia/diagnosis
20.
Biol Psychiatry ; 30(5): 475-82, 1991 Sep 01.
Article in English | MEDLINE | ID: mdl-1932395

ABSTRACT

The relationship of plasma free homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) to early clinical response was prospectively studied in a new series of acutely psychotic inpatients given a fixed dose of perphenazine elixir for 10 days. Elevated pretreatment plasma HVA but not MHPG was significantly associated with good response. Change in HVA was correlated with a favorable response and a significant decline in MHPG was found in responders. Results suggest that HVA can provide a useful clinical predictor of response, and that both dopamine metabolism and noradrenergic functioning, as measured by plasma HVA and MHPG, are reduced in effective neuroleptic treatment.


Subject(s)
Homovanillic Acid/blood , Methoxyhydroxyphenylglycol/blood , Perphenazine/administration & dosage , Psychiatric Status Rating Scales , Psychotic Disorders/blood , Psychotic Disorders/drug therapy , Acute Disease , Adolescent , Adult , Bipolar Disorder/blood , Bipolar Disorder/drug therapy , Bipolar Disorder/psychology , Chromatography, High Pressure Liquid , Depressive Disorder/blood , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Psychotic Disorders/psychology , Schizophrenia/blood , Schizophrenia/drug therapy , Schizophrenic Psychology
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