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P Jatlow

Publications and source records attributed to P Jatlow.

At least 37 records · Page 2Linked to original sources
PubMed1996

Rapid high-performance liquid chromatographic assay for atovaquone.

A rapid high-performance liquid chromatography assay has been developed for the drug atovaquone, which is currently being used to treat Pneumocystis carinii pneumonia and Toxoplasma gondii encephalitis associated with the acquired immunodeficiency syndrome (AIDS). Protein is precipitated from plasma with acetonitrile-aqueous 1% acetic acid (85:15). The supernatant is assayed on a C6 column using methanol-10 mM triethylamine in aqueous 0.2% trifluoroacetic acid (76:24) with detection at 254 nm. The working assay range was 0.5 to 50 micrograms/ml. Recovery was 97% and the between-day coefficients of variation were 2.1% at 50 micrograms/ml and 10.3% at 1 microgram/ml. A number of drugs commonly used to treat AIDS and its complications did not interfere with the assay.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Alcohol plus cocaine: the whole is more than the sum of its parts.

Cocaethylene, an active metabolite that arises through hepatic transesterification of cocaine when cocaine and ethanol are used together, shares many neurochemical and pharmacological properties with cocaine. Cocaethylene is similar to cocaine in its properties as an indirect dopamine agonist, and human subjects cannot distinguish its effects from those of cocaine. Cocaethylene, and especially its isopropyl analog, are more selective indirect dopamine agonists than cocaine, with relatively weak potency at the serotonin transporter. Cocaethylene may contribute to the manifestations and consequences of combined cocaine and ethanol use, although its relative importance remains unclear.

Central Nervous System Depressants↗
PubMed1995

Serotonergic mechanisms of cocaine effects in humans.

The objective of this study was to investigate the role of serotonin (5-HT) in mediating the effects of cocaine in humans. To accomplish this, 12 subjects each participated in two randomized, double-blind test sessions separated by 1 week. In one session, subjects underwent acute depletion of the 5-HT amino acid precursor tryptophan (TRP), followed by a test dose of intranasal cocaine. In the other session, the cocaine test dose was preceded by sham depletion. Subject ratings of cocaine "high" were significantly lower following active TRP depletion than after the sham procedure. Subjects also showed an earlier but less sustained rise in self-rated nervousness during active TRP depletion. These findings are consistent with the hypothesis that 5-HT may be involved in mediating the euphorigenic and modulating the anxiogenic effects of cocaine in humans, either directly or through actions on other (e.g., dopaminergic) systems.

Adult↗
PubMed1994

Psychotherapy and pharmacotherapy for ambulatory cocaine abusers.

BACKGROUND: At present, there is no consensus regarding effective treatment for cocaine abuse or the most productive roles for the two major forms of treatment, pharmacotherapy and psychotherapy. We conducted the first randomized clinical trial evaluating psychotherapy and pharmacotherapy, alone and in combination, as treatment for ambulatory cocaine abusers. METHODS: One hundred thirty-nine subjects were assigned to one of four conditions offered over a 12-week abstinence initiation trial: relapse prevention plus desipramine hydrochloride, clinical management plus desipramine, relapse prevention plus placebo, and clinical management plus placebo. All treatments were manual-guided, delivered by experienced therapists, and monitored to promote the integrity of both forms of treatment. RESULTS: First, although all groups showed significant improvement, significant main effects for medication or psychotherapy, or their combination, were not found for treatment retention, reduction in cocaine use, or other outcomes at 12 weeks. Second, baseline severity of cocaine use interacted differently with psychotherapy and pharmacotherapy: higher-severity patients had significantly better outcome when treated with relapse prevention than with clinical management, while desipramine was associated with improved abstinence initiation among lower-severity subjects. Third, desipramine was significantly more effective than placebo in reducing cocaine use over 6, but not 12, weeks of treatment. Fourth, depressed subjects had greater reduction in cocaine use than nondepressed subjects and had better response to relapse prevention than to clinical management. CONCLUSION: These findings underscore the significance of heterogeneity among cocaine abusers and the need to develop specialized treatments for clinically distinct subgroups of cocaine abusers.

Adult↗
PubMed1993

Cocaine and cocaethylene: microdialysis comparison of brain drug levels and effects on dopamine and serotonin.

Cocaethylene is a pharmacologically active metabolite resulting from concurrent cocaine and ethanol consumption. The effects of cocaine and cocaethylene on extracellular levels of dopamine in the nucleus accumbens, and serotonin in the striatum were characterized in vivo in the anesthetized rat. Both intravenous (3 mumol/kg) and intraperitoneal (44 mumol/kg) routes of administration were used. In addition to monitoring neurotransmitter levels, microdialysate levels of cocaine and cocaethylene were determined at 4-min intervals after intravenous administration, and at 20-min intervals after intraperitoneal administration. Extracellular levels of dopamine in the nucleus accumbens were increased to approximately 400% of preinjection value by both cocaine and cocaethylene when administered intravenously. Cocaine caused a significant increase of striatal serotonin to 200% preinjection value, whereas cocaethylene had no effect. Brain levels of cocaine and cocaethylene after intravenous administration did not differ. After intraperitoneal administration, extracellular levels of dopamine in the nucleus accumbens were increased to 400% of preinjection levels by cocaine, but were only increased to 200% of preinjection levels by cocaethylene, the difference being statistically significant. Serotonin levels were increased to 360% of preinjection levels by cocaine, but only to 175% of preinjection value by cocaethylene. Levels of cocaine attained in brain were significantly higher than those for cocaethylene, suggesting pharmacokinetic differences with the intraperitoneal route. These results confirm in vivo that cocaethylene is more selective in its actions than cocaine with respect to dopamine and serotonin uptake. In addition, route-dependent differences in attainment of brain drug levels have been observed that may impact on interpretations of the relative potency of the reinforcement value of these compounds.

Animals↗
PubMed1993

Cocaethylene: pharmacologic activity and clinical significance.

Consumption of ethanol during the course of cocaine binges is common, with an estimated prevalence well in excess of 50%. Cocaine abusers indicate that coingestion of ethanol may enhance and/or prolong the euphoria and reduce unpleasant side effects that may follow. Cocaethylene, an active homologue/metabolite that arises through transesterification of cocaine following coconsumption of cocaine and alcohol, shares many neurochemical and behavioral properties with cocaine and reaches significant blood concentrations. However, cocaine and cocaethylene also appear to differ in some respects, including the relative potency of their actions on the dopamine and serotonin transporters. Information obtained from animal and human studies of the neurochemical and behavioral properties of cocaethylene and of cocaine-ethanol interactions is reviewed, and the possible implications with respect to the mechanisms and consequences of combined cocaine and ethanol abuse are described.

Animals↗
PubMed1992

Intravenous cocaine challenges during desipramine maintenance.

Intravenous challenges with placebo and cocaine doses ranging from 0.125 to 0.5 mg/kg were administered to five subjects using a within subjects design during placebo and active desipramine (DMI) maintenance at a fixed dose of 150 mg daily for at least 10 days. The "high" reported after cocaine infusion was not altered by DMI, but "desire for cocaine" after a single dose was attenuated. Together with the results of clinical trials of DMI for cocaine abuse, these laboratory results suggest that DMI may reduce cocaine craving both during and between cocaine binges. Physiologically, baseline heart rate was higher on DMI, but the incremental heart rate response to cocaine was attenuated.

Adult↗
PubMed1991

Cocaethylene: a neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion.

High concentrations of cocaethylene (EC), the ethyl ester of benzoylecgonine, were measured in the blood of individuals who had concurrently used cocaine and ethanol. Since the powerful reinforcing effects of cocaine appear to be dependent on inhibition of dopamine reuptake in brain, we compared the effects of EC on the dopamine uptake system and its behavioral effects with those of cocaine. EC was equipotent to cocaine with respect to inhibition of binding of [3H]GBR 12935 to the dopamine reuptake complex, inhibition of [3H]dopamine uptake into synaptosomes and in its ability to increase extracellular dopamine concentration in the nucleus accumbens following its systemic administration to rats. Moreover, in rats, EC and cocaine each increased locomotor activity and rearing to the same extent following i.p. administration. In self-administration studies in primates, EC was approximately equipotent to cocaine in maintaining responding. The in vivo formation of this active, transesterified ethyl homolog of cocaine may contribute to the effects and consequences of combined cocaine and ethanol abuse.

Analysis of Variance↗
PubMed1990

Growth hormone and prolactin response to methylphenidate in children with attention deficit disorder.

Utilizing a double-blind, drug-placebo design, we examined growth hormone (GH) and prolactin (Pro) response to oral administration of methylphenidate (MPH) in 14 boys (ages 7.0-12.4 years) with Attention Deficit Disorder (ADD). Four conditions representing three different MPH doses (0.3 mg/kg O.D., 0.3 mg/kg B.I.D., 0.6 mg/kg O.D.) and Placebo were compared in each subject, each condition lasting for a period of 3 weeks. GH and Pro response were measured both as maximum peak GH (DGH) or nadir of Pro (DPro) as well as area under the curve for the first four hours after MPH administration (AUCGH, AUCPro). Behavioral measures included parent ratings on the Yale Children's Inventory and teacher ratings on the Yale and Conners Behavior Rating Scales and Kagan's Matching Familiar Figures Test (MFFT). Prolactin response as measured by AUCPro was significantly increased after MPH compared to placebo (t = 2.04, p less than 0.05, placebo vs all doses MPH). This difference observed for AUCPro between placebo and MPH was evident as well when we considered the number of times AUCPro declined after MPH as compared to placebo (p = .018, Fisher's exact test). Within-subjects analysis of covariance demonstrated significant correlations between the improvement in reaction time on the MFFT and 1) GH response (AUCGH, r = .58, p less than .001) and 2) prolactin response (AUCPro, r = .40, p less than .05) and between improvement in attention as measured on the Yale BRS and GH response (AUCGH, r = .57, p less than .05). Our findings suggest that measures other than GH and prolactin may be more desirable measures of brain catecholaminergic functioning.

Attention Deficit Disorder with Hyperactivity↗
PubMed1990

Evidence for altered desipramine disposition in methadone-maintained patients treated for cocaine abuse.

Plasma concentrations of desipramine (DMI) and its 2-hydroxy metabolite (OHDMI) were compared among 72 patients being treated with desipramine for either depression (n = 39) or cocaine abuse (n = 33). Eleven cocaine abusers who were concurrently maintained on methadone had a significantly lower ratio of DMI dose to plasma concentration (0.9) than the depressives (2.2) or nonmethadone cocaine abusers (2.0). Their OHDMI/DMI ratios were significantly lower (0.19) than for either the other 22 cocaine abusers (0.39) or the depressed (0.50) patients. This difference was not due to DMI dosage. Although the underlying mechanism cannot be determined from these plasma studies, possible reduced hydroxylation of DMI in methadone patients suggests the need for DMI plasma monitoring.

Adult↗