Possible novel pharmacodynamic action of cocaine: Cardiovascular and behavioral evidence

Tella, Srihari R.

doi:10.1016/0091-3057(95)02145-0

Cited by 27 publications

(21 citation statements)

References 57 publications

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“…Fixed ratio intravenous drug self-administration experiments were performed according to the procedure described previously (Tella et al, 1996). Briefly, male Sprague-Dawley rats (n ϭ 7-9/group) were trained to lever press for food under a fixed ratio 10 schedule during 1-h daily sessions.…”

Section: Methodsmentioning

confidence: 99%

“…There is some evidence suggesting the possible involvement of additional pharmacodynamic mechanisms in cocaine's actions (Sherer et al, 1989;Price et al, 1995Price et al, , 1997Rothman and Glowa, 1995;Tella 1996;Stine et al, 1995;Rocha et al, 1998;Sora et al, 1998;Tella and Goldberg, 1998;Volkow et al, 1999). In this context, it has been suggested that serotonin transporter (SERT)-dependent effects may play some role in cocaine addiction (Rocha et al, 1998;Tran-Nguyen et al, 1999;Belzung et al, 2000).…”

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confidence: 99%

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Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Kozikowski

Johnson²,

Deschaux

et al. 2003

J Pharmacol Exp Ther

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The present study investigated the pharmacological properties of a piperidine-based novel cocaine analog, namely, (ϩ)-methyl 4␤-(4-chlorophenyl)-1-methylpiperidine-3␣-carboxylic acid [(ϩ)-CPCA]. Like cocaine, (ϩ)-CPCA inhibited rat synaptosomal dopamine and norepinephrine uptake with high affinity, but was 33-fold less potent than cocaine in inhibiting serotonin uptake. Like cocaine, (ϩ)-CPCA is a locomotor stimulant, although it was less potent and efficacious than cocaine. Importantly, pretreatment with (ϩ)-CPCA dose dependently blocked the locomotor stimulant effects of cocaine in rats. (ϩ)-CPCA completely substituted for cocaine in drug discrimination tests, although it was about 3 times less potent than cocaine. It was also self-administered by rats. Unexpectedly, (ϩ)-CPCA did not enhance cocaine-induced convulsions in mice. As expected from rodent studies, rhesus monkeys readily self-administered (ϩ)-CPCA. However, compared with cocaine, (ϩ)-CPCA showed limited reinforcing properties in rats as assessed by both fixed and progressive ratio intravenous drug self-administration tests. These results collectively suggest that (ϩ)-CPCA has an atypical pharmacological profile having both cocaine-like "agonist" and some cocaine "antagonist" properties. These properties of (ϩ)-CPCA suggest that it may have utility in the treatment of cocaine craving and dependence.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Kozikowski

Johnson²,

Deschaux

et al. 2003

J Pharmacol Exp Ther

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“…Tella (1996) showed that GBR 12909 produced a prolonged increase in blood pressure and heart rate in conscious rats, although Knuepfer and Gan (1997) failed to show a similar effect. Quinpirole decreases blood pressure in a number of conscious animal models (e.g., Nagahama et al, 1986).…”

Section: Discussionmentioning

confidence: 99%

Interactions between Cocaine and Dopamine Agonists on Cardiovascular Function in Squirrel Monkeys

Schindler

Gilman²,

Bergman³

et al. 2002

J Pharmacol Exp Ther

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Conscious squirrel monkeys were treated i.v. with cocaine and various dopamine agonist drugs. Cocaine produced a dose-dependent increase in blood pressure, heart rate, and the rate-pressure product (RPP). The dopamine D1 receptor agonist (Ϯ)-6-chloro-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 82958) produced effects comparable to cocaine. The D1 agonist (Ϯ)-6-chloro-7, 8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) also produced increases in blood pressure and heart rate but was much less potent than either cocaine or SKF 82958. The partial D1 agonist (Ϯ)-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SKF 77434) did not significantly affect any cardiovascular parameters. The D2 agonist quinpirole slightly decreased blood pressure and increased heart rate. As such, the RPP only slightly increased. The selective dopamine uptake inhibitor 1-[2-[bis-(4-fluorphenyl)methoxy-]ethyl]-4-(3-phenylpropyl)piperazine (GBR 12909) produced increases in blood pressure, heart rate, and RPP, but again these effects were smaller and only seen at doses higher than cocaine. Effects similar to those with GBR 12909 were seen with the dopamine autoreceptor antagonist cis-(ϩ)-5-methoxy-1-methyl-2-(di-n-propylamino)tetralin (UH 232). The combination of GBR 12909, SKF 82958, or SKF 77434 with cocaine produced effects that were clearly subadditive. The effects of quinpirole in combination with cocaine were comparable to, or lower than, those of cocaine alone on blood pressure and RPP. The effects on heart rate were additive. Only UH 232 produced additive effects with cocaine for all three measures. As dopamine agonists have been proposed as potential treatments for cocaine abuse, these results suggest that dopamine D1 agonists and uptake inhibitors can be used safely in combination with cocaine.

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“…Rats were surgically prepared with a plastic skull pedestal, a jugular vein catheter, and transducers for measuring blood pressure, heart rate, locomotor activity, and temperature [Tella et al, 1996]. In addition, two leads for measuring the electrocardiogram using the lead II position were implanted.…”

Section: Surgical Procedures and Telemetry Systemmentioning

confidence: 99%

Pharmacology, toxicology, and radiation dosimetry evaluation of [¹²³I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans

Vaupel

Tella

Huso

et al. 2003

Drug Development Research

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[123 I]5-I-A-85380, which selectively binds to a4b2 nicotinic acetylcholine receptors, may be a suitable single photon emission computed tomography (SPECT) ligand for imaging nicotinic receptors in the human brain. In a mutagenicity study, 5-I-A-85380 produced positive effects in one of five bacterial strains in the bacterial reverse mutation assay only with metabolic activation. The ED 50 for 5-I-A-85380 to elicit tonicclonic convulsions in mice, 7.1 mmol/kg, i.v., was five times that of nicotine (ED 50 ¼ 1.4 mmol/kg, i.v.). A 2-day acute toxicity study (0.03-150 nmol/kg, i.v.) and a 14-day chronic toxicity study (0.3-30 nmol/kg, s.c.) in mice revealed no evidence of gross pathology or histopathological changes. Biodistribution and dosimetry studies revealed that the urinary bladder wall and the thyroid gland were the critical organs with respect to radiation exposure. In unanesthetized rats, 5-I-A-85380 (5.2-174 nmol/kg, i.v.) and nicotine (20-400 nmol/kg, i.v.) produced similar increases in systolic and diastolic blood pressure, heart rate, and locomotor activity. Doses of 5-I-A-85380 that elevated blood pressure and heart rate by 10% ranged from 5-10 nmol/kg, i.v. The highest doses tested, which produced near maximal increases in blood pressure and heart rate, did not affect the PR, QRS, or QTc intervals of the electrocardiogram. Based on these preclinical data, initial SPECT imaging studies in humans (Fujita et al. [2002] Eur J Nucl Med 29:183-190) used a mass dose of 8.6 pmol/kg [ 123 I]5-I-A-8380, estimated to be 1/580th of the dose that elevates blood pressure and heart rate by 10%. Importantly, no clinical pharmacological effects were observed. Drug Dev.

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Possible novel pharmacodynamic action of cocaine: Cardiovascular and behavioral evidence

Cited by 27 publications

References 57 publications

Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Interactions between Cocaine and Dopamine Agonists on Cardiovascular Function in Squirrel Monkeys

Pharmacology, toxicology, and radiation dosimetry evaluation of [¹²³I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans

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Possible novel pharmacodynamic action of cocaine: Cardiovascular and behavioral evidence

Cited by 27 publications

References 57 publications

Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Mixed Cocaine Agonist/Antagonist Properties of (+)-Methyl 4β-(4-Chlorophenyl)-1-methylpiperidine-3α-carboxylate, a Piperidine-Based Analog of Cocaine

Interactions between Cocaine and Dopamine Agonists on Cardiovascular Function in Squirrel Monkeys

Pharmacology, toxicology, and radiation dosimetry evaluation of [123I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans

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Product

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Pharmacology, toxicology, and radiation dosimetry evaluation of [¹²³I]5‐I‐A‐85380, a radioligand for in vivo imaging of cerebral neuronal nicotinic acetylcholine receptors in humans