Transdermal selegiline and intravenous cocaine: safety and interactions

Houtsmuller, Elisabeth J.; Notes, Lisa D.; Newton, Thomas F.; Sluis, Nicolette van; Chiang, Nora; Elkashef, Ahmed; Bigelow, George E.

doi:10.1007/s00213-003-1616-6

Cited by 31 publications

(21 citation statements)

References 50 publications

(48 reference statements)

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“…Only tranylcypromine, a non-selective MAO inhibitor, failed to produce any reduction in cocaine-appropriate responding. The magnitude of the effects were small, in agreement with earlier studies in humans in which selegiline attenuated the subjective and/or discriminative stimulus effects of cocaine (Bartzokis et al, 1999;Houtsmuller et al, 2004). The present study used a fairly large training dose of cocaine, so it is possible that these compounds could fully block the discriminative stimulus effects of lower doses of cocaine.…”

Section: Effects 24 To 48 Hours After Administrationsupporting

confidence: 90%

“…of cocaine. In addition, selegiline reversed the effects of cocaine on glucose utilization in the amygdala as measured by PET scans (Bartzokis et al, 1999) but did not alter metabolism of cocaine nor cocaine's effects on prolactin or growth hormone (Houtsmuller et al, 2004). Such findings suggest that MAO inhibitors might be good candidates as potential treatments of cocaine abuse and dependence.…”

mentioning

confidence: 83%

“…Selegiline, an irreversible MAO-B selective inhibitor (Salach et al, 1979), decreased the subjective effects of cocaine in human subjects (Bartzokis et al, 1999;Houtsmuller et al, 2004). Treatment with 10 to 20 mg of selegiline for 6 to 10 days reduced subjects' ratings of being "high" by 40% following 20 or 40 mg (i.v.)…”

mentioning

confidence: 99%

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Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Gatch

Taylor

Flores

et al. 2006

Behavioural Pharmacology

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This study tested the time course of the discriminative stimulus effects of inhibitors of monoamine oxidase (MAO) alone or in combination with cocaine. Male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline using a two-lever choice methodology. The nonselective MAO inhibitors tranylcypromine (0.01 to 5 mg/kg) and phenelzine (1 to 25 mg/kg), the MAO-A selective compound clorgyline (1 to 25 mg/kg), and the MAO-B selective compounds pargyline (0.005 to 50 mg/kg) and selegiline (1 to 25 mg/kg) were tested for substitution 15 min or 24 hr following administration, and in combination with 10 mg/kg of cocaine 24 and 48 hr after administration. At 15 min, selegiline fully substituted for the discriminative stimulus effects of cocaine, whereas all other compounds partially substituted. At 24 hr, substitution of cocaine was diminished for all compounds except phenelzine, which produced a greater amount of substitution at 24 hr than at 15 min. When cocaine was administered 24 hr following clorgyline, selegiline, pargyline, and phenelzine, cocaine-appropriate responding was attenuated at intermediate doses of these drugs, whereas the highest doses did not alter cocaine-lever responding. All compounds except selegiline substantially decreased response rate and produced various adverse effects. At 48 hr, the effects of all compounds except phenelzine were markedly reduced. Selectivity for MAO-A or B did not predict the ability to substitute for or attenuate the subjective effects of cocaine. These findings suggest that MAO inhibitors can modulate the discriminative stimulus effects of cocaine for at least 24 hr, and may be useful for treatment of cocaine abuse.

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Section: Effects 24 To 48 Hours After Administrationsupporting

confidence: 90%

mentioning

confidence: 83%

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Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Gatch

Taylor

Flores

et al. 2006

Behavioural Pharmacology

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“…14 A signifi cant component of this effort is to rapidly screen currently marketed drugs to identify potential lead compounds for further testing. Of the compounds tested, 4 (cabergoline, 15 reserpine, 16 sertraline, 17 and tiagabine 18 ) have been advanced to further phase II clinical trials, and 2 others (disulfi ram 19 and selegiline 20 ) have proceeded or are soon expected to proceed to phase III trials. Other compounds, including baclofen, 21 topiramate, 22 and modafi nil 23 have also advanced into midstage clinical development.…”

Section: Cocaine Pharmacotherapymentioning

confidence: 99%

RETRACTED ARTICLE: Recent advances for the treatment of cocaine abuse: Central nervous system immunopharmacotherapy

Dickerson

Janda

2005

AAPS J

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A BSTRACTCocaine addiction continues to be a major health and societal problem in spite of governmental efforts devoted toward educating the public of the dangers of illicit drug use. A variety of pharmacotherapies and psychosocial programs have been proposed in an effort to provide a method for alleviation of the physical and psychological symptoms of cocaine abuse. Unfortunately, these methods have been met with limited success, illustrating a critical need for new effective approaches for the treatment of cocaine addiction. Recently an alternative cocaine abuse treatment strategy was proposed using intranasal administration of an engineered fi lamentous bacteriophage displaying cocaine-sequestering antibodies on its surface. These phage particles are an effective vector for CNS penetration and are capable of binding cocaine, thereby blocking its behavioral effects in a rodent model. The convergence of phage display and immunopharmacotherapy has allowed for an investigation of the effi cacy of protein-based therapeutics acting within the CNS on the effects of cocaine in animal models and has uncovered a new tool in the battle against cocaine addiction.

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“…(R)-(Ϫ)-Deprenyl has also been proposed as a cognitive enhancer (Gelowitz et al, 1994), as a treatment for attention deficit hyperactivity disorder (Akhondzadeh et al, 2003), as a treatment for drug dependence (Grasing and Ghosh, 1998;Houtsmuller et al, 2004), and as an aid for smoking cessation (George et al, 2003).…”

Section: L-deprenyl [Selegiline (R)-(ϫ)-deprenyl] a Selective Inhibmentioning

confidence: 99%

Metabolic Transformation Plays a Primary Role in the Psychostimulant-Like Discriminative-Stimulus Effects of Selegiline [(R)-(–)-Deprenyl]

Yaşar¹,

Justinová²,

Lee³

et al. 2005

J Pharmacol Exp Ther

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Transdermal selegiline and intravenous cocaine: safety and interactions

Abstract: The combined administration of the transdermal selegiline patch and up to 40 mg cocaine was well tolerated. Selegiline may reduce physiological and subjective effects of cocaine. A randomized trial is needed to evaluate the efficacy of selegiline for cocaine abuse.

Cited by 31 publications

References 50 publications

Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

Effects of monoamine oxidase inhibitors on cocaine discrimination in rats

RETRACTED ARTICLE: Recent advances for the treatment of cocaine abuse: Central nervous system immunopharmacotherapy

Metabolic Transformation Plays a Primary Role in the Psychostimulant-Like Discriminative-Stimulus Effects of Selegiline [(R)-(–)-Deprenyl]

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