The Experts below are selected from a list of 273 Experts worldwide ranked by ideXlab platform
Bankole A. Johnson - One of the best experts on this subject based on the ideXlab platform.
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Effects of repeated-dose Isradipine on the abuse liability of cocaine.
Experimental and clinical psychopharmacology, 2005Co-Authors: John D. Roache, Bankole A. Johnson, Lynda T. Wells, Nassima Ait-daoud, James B. Mauldin, Joe E. Thornton, William L. MurffAbstract:Despite preclinical studies suggesting that Isradipine may antagonize the abuse liability of cocaine, pretreatment with sustained-release Isradipine did not reduce euphoric mood in cocaine-using volunteers. This double-blind, within-subject, crossover laboratory study determined whether maximal dose-loading with Isradipine could antagonize effects of cocaine in 12 cocaine-dependent research volunteers administered intravenous cocaine doses (0, 0.325, and 0.65 mg/kg) on different days after 5 days of treatment with Isradipine or placebo. Isradipine dose was 30 mg sustained release nightly plus 15 mg immediate release 2 hr before cocaine infusion. Cocaine produced dose-related increases in cocaine's subjective effects and a behavioral measure of reinforcement. Isradipine enhanced, rather than antagonized, subjective effects, indicating that Isradipine does not antagonize cocaine's abuse liability in dependent research volunteers.
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Kinetic and cardiovascular comparison of immediate-release Isradipine and sustained-release Isradipine among non-treatment-seeking, cocaine-dependent individuals.
Progress in neuro-psychopharmacology & biological psychiatry, 2004Co-Authors: Bankole A. Johnson, Martin A. Javors, Yui Wing Francis Lam, Lynda T. Wells, Mohamed Tiouririne, John D. Roache, Nassima Ait-daoud, Kevin LawsonAbstract:The authors sought to determine whether sustained-release (SR) Isradipine provided comparable systemic availability to that of immediate-release (IR) Isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional Isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR Isradipine formulation and a 30-mg dose of an SR Isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for Isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each Isradipine dose administration. Neither the 15-mg dose of IR Isradipine nor the 30-mg dose of SR Isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR Isradipine achieves a higher peak concentration than SR Isradipine. The more favorable cardiovascular profile of SR Isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.
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Effects of Isradipine on cocaine-induced subjective mood.
Journal of clinical psychopharmacology, 2004Co-Authors: Bankole A. Johnson, Lynda T. Wells, John D. Roache, Nassima Ait-daoud, James B. MauldinAbstract:We hypothesized that in humans, as in animals, Isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that Isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make Isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose Isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without Isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR Isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher Isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, Isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.
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Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans
Neuropsychopharmacology, 2000Co-Authors: Bankole A. Johnson, Nassima Ait-daoud, Lynda T. WellsAbstract:D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of Isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by Isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.
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Isradipine a dihydropyridine class calcium channel antagonist attenuates some of d methamphetamine s positive subjective effects a preliminary study
Psychopharmacology, 1999Co-Authors: Bankole A. Johnson, John D. Roache, Patrick S Bordnick, Nassima AitdaoudAbstract:Rationale: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine’s rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by Isradipine. Objective: We studied the effects of high dose Isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). Methods: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2–7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose Isradipine+placebo); e) low-dose d-methamphetamine+high dose Isradipine, and f) high-dose d-methamphetamine+high dose Isradipine. Results: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with Isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. Conclusion: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.
Lynda T. Wells - One of the best experts on this subject based on the ideXlab platform.
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Effects of repeated-dose Isradipine on the abuse liability of cocaine.
Experimental and clinical psychopharmacology, 2005Co-Authors: John D. Roache, Bankole A. Johnson, Lynda T. Wells, Nassima Ait-daoud, James B. Mauldin, Joe E. Thornton, William L. MurffAbstract:Despite preclinical studies suggesting that Isradipine may antagonize the abuse liability of cocaine, pretreatment with sustained-release Isradipine did not reduce euphoric mood in cocaine-using volunteers. This double-blind, within-subject, crossover laboratory study determined whether maximal dose-loading with Isradipine could antagonize effects of cocaine in 12 cocaine-dependent research volunteers administered intravenous cocaine doses (0, 0.325, and 0.65 mg/kg) on different days after 5 days of treatment with Isradipine or placebo. Isradipine dose was 30 mg sustained release nightly plus 15 mg immediate release 2 hr before cocaine infusion. Cocaine produced dose-related increases in cocaine's subjective effects and a behavioral measure of reinforcement. Isradipine enhanced, rather than antagonized, subjective effects, indicating that Isradipine does not antagonize cocaine's abuse liability in dependent research volunteers.
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Kinetic and cardiovascular comparison of immediate-release Isradipine and sustained-release Isradipine among non-treatment-seeking, cocaine-dependent individuals.
Progress in neuro-psychopharmacology & biological psychiatry, 2004Co-Authors: Bankole A. Johnson, Martin A. Javors, Yui Wing Francis Lam, Lynda T. Wells, Mohamed Tiouririne, John D. Roache, Nassima Ait-daoud, Kevin LawsonAbstract:The authors sought to determine whether sustained-release (SR) Isradipine provided comparable systemic availability to that of immediate-release (IR) Isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional Isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR Isradipine formulation and a 30-mg dose of an SR Isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for Isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each Isradipine dose administration. Neither the 15-mg dose of IR Isradipine nor the 30-mg dose of SR Isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR Isradipine achieves a higher peak concentration than SR Isradipine. The more favorable cardiovascular profile of SR Isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.
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Effects of Isradipine on cocaine-induced subjective mood.
Journal of clinical psychopharmacology, 2004Co-Authors: Bankole A. Johnson, Lynda T. Wells, John D. Roache, Nassima Ait-daoud, James B. MauldinAbstract:We hypothesized that in humans, as in animals, Isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that Isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make Isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose Isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without Isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR Isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher Isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, Isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.
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Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans
Neuropsychopharmacology, 2000Co-Authors: Bankole A. Johnson, Nassima Ait-daoud, Lynda T. WellsAbstract:D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of Isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by Isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.
John D. Roache - One of the best experts on this subject based on the ideXlab platform.
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Effects of repeated-dose Isradipine on the abuse liability of cocaine.
Experimental and clinical psychopharmacology, 2005Co-Authors: John D. Roache, Bankole A. Johnson, Lynda T. Wells, Nassima Ait-daoud, James B. Mauldin, Joe E. Thornton, William L. MurffAbstract:Despite preclinical studies suggesting that Isradipine may antagonize the abuse liability of cocaine, pretreatment with sustained-release Isradipine did not reduce euphoric mood in cocaine-using volunteers. This double-blind, within-subject, crossover laboratory study determined whether maximal dose-loading with Isradipine could antagonize effects of cocaine in 12 cocaine-dependent research volunteers administered intravenous cocaine doses (0, 0.325, and 0.65 mg/kg) on different days after 5 days of treatment with Isradipine or placebo. Isradipine dose was 30 mg sustained release nightly plus 15 mg immediate release 2 hr before cocaine infusion. Cocaine produced dose-related increases in cocaine's subjective effects and a behavioral measure of reinforcement. Isradipine enhanced, rather than antagonized, subjective effects, indicating that Isradipine does not antagonize cocaine's abuse liability in dependent research volunteers.
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Kinetic and cardiovascular comparison of immediate-release Isradipine and sustained-release Isradipine among non-treatment-seeking, cocaine-dependent individuals.
Progress in neuro-psychopharmacology & biological psychiatry, 2004Co-Authors: Bankole A. Johnson, Martin A. Javors, Yui Wing Francis Lam, Lynda T. Wells, Mohamed Tiouririne, John D. Roache, Nassima Ait-daoud, Kevin LawsonAbstract:The authors sought to determine whether sustained-release (SR) Isradipine provided comparable systemic availability to that of immediate-release (IR) Isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional Isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR Isradipine formulation and a 30-mg dose of an SR Isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for Isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each Isradipine dose administration. Neither the 15-mg dose of IR Isradipine nor the 30-mg dose of SR Isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR Isradipine achieves a higher peak concentration than SR Isradipine. The more favorable cardiovascular profile of SR Isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.
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Effects of Isradipine on cocaine-induced subjective mood.
Journal of clinical psychopharmacology, 2004Co-Authors: Bankole A. Johnson, Lynda T. Wells, John D. Roache, Nassima Ait-daoud, James B. MauldinAbstract:We hypothesized that in humans, as in animals, Isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that Isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make Isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose Isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without Isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR Isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher Isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, Isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.
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Isradipine a dihydropyridine class calcium channel antagonist attenuates some of d methamphetamine s positive subjective effects a preliminary study
Psychopharmacology, 1999Co-Authors: Bankole A. Johnson, John D. Roache, Patrick S Bordnick, Nassima AitdaoudAbstract:Rationale: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine’s rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by Isradipine. Objective: We studied the effects of high dose Isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). Methods: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2–7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose Isradipine+placebo); e) low-dose d-methamphetamine+high dose Isradipine, and f) high-dose d-methamphetamine+high dose Isradipine. Results: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with Isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. Conclusion: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.
Nassima Ait-daoud - One of the best experts on this subject based on the ideXlab platform.
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Effects of repeated-dose Isradipine on the abuse liability of cocaine.
Experimental and clinical psychopharmacology, 2005Co-Authors: John D. Roache, Bankole A. Johnson, Lynda T. Wells, Nassima Ait-daoud, James B. Mauldin, Joe E. Thornton, William L. MurffAbstract:Despite preclinical studies suggesting that Isradipine may antagonize the abuse liability of cocaine, pretreatment with sustained-release Isradipine did not reduce euphoric mood in cocaine-using volunteers. This double-blind, within-subject, crossover laboratory study determined whether maximal dose-loading with Isradipine could antagonize effects of cocaine in 12 cocaine-dependent research volunteers administered intravenous cocaine doses (0, 0.325, and 0.65 mg/kg) on different days after 5 days of treatment with Isradipine or placebo. Isradipine dose was 30 mg sustained release nightly plus 15 mg immediate release 2 hr before cocaine infusion. Cocaine produced dose-related increases in cocaine's subjective effects and a behavioral measure of reinforcement. Isradipine enhanced, rather than antagonized, subjective effects, indicating that Isradipine does not antagonize cocaine's abuse liability in dependent research volunteers.
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Kinetic and cardiovascular comparison of immediate-release Isradipine and sustained-release Isradipine among non-treatment-seeking, cocaine-dependent individuals.
Progress in neuro-psychopharmacology & biological psychiatry, 2004Co-Authors: Bankole A. Johnson, Martin A. Javors, Yui Wing Francis Lam, Lynda T. Wells, Mohamed Tiouririne, John D. Roache, Nassima Ait-daoud, Kevin LawsonAbstract:The authors sought to determine whether sustained-release (SR) Isradipine provided comparable systemic availability to that of immediate-release (IR) Isradipine in non-treatment-seeking, cocaine-dependent individuals. This information could be used to design a rational dosage regimen for additional Isradipine clinical trials in the treatment of stimulant dependence and related neurovascular disorders. Eight male volunteers who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a randomized, double-blind, crossover study. Subjects received a 15-mg dose of an IR Isradipine formulation and a 30-mg dose of an SR Isradipine formulation, separated by a 2-day interval. Vital signs and blood sampling for Isradipine serum levels were performed before and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, and 24 h after each Isradipine dose administration. Neither the 15-mg dose of IR Isradipine nor the 30-mg dose of SR Isradipine produced significant adverse effects on cardiovascular parameters, but the IR formulation was more likely to produce marked short-term decreases in pressor response. Significant intersubject variability in serum concentrations and pharmacokinetic parameters occurred for both formulations. The relative bioavailability of the SR formulation was 55.5% of that of the IR formulation. Both formulations cumulatively may deliver about the same amount of drug, but IR Isradipine achieves a higher peak concentration than SR Isradipine. The more favorable cardiovascular profile of SR Isradipine would, however, make it more appropriate as an investigational medication for the treatment of stimulant dependence and related neurovascular disorders.
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Effects of Isradipine on cocaine-induced subjective mood.
Journal of clinical psychopharmacology, 2004Co-Authors: Bankole A. Johnson, Lynda T. Wells, John D. Roache, Nassima Ait-daoud, James B. MauldinAbstract:We hypothesized that in humans, as in animals, Isradipine, a dihydropyridine-class calcium channel antagonist, would antagonize cocaine's rewarding effects, based on preclinical evidence that Isradipine inhibits cocaine-mediated increases in mesolimbic dopamine (DA), thereby reducing cocaine's abuse liability. Confirmation of our hypothesis would make Isradipine a promising medication for treating cocaine dependence. Eighteen male and female volunteers (mean age, 32.6 years) who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for cocaine dependence participated in a double-blind, placebo-controlled, crossover study. Subjects received placebo or sustained-release (SR) low-dose or high-dose Isradipine (15 or 30 mg), plus placebo or low-dose or high-dose cocaine HCl (0.325 or 0.650 mg/kg), for 9 treatment sessions separated by a 2-day interval. Standardized assessments of abuse liability, including a choice procedure to determine preference for cocaine with and without Isradipine over monetary incentives, were conducted at scheduled intervals. Cocaine administration produced dose-related prototypic increases in stimulant-related effects, including euphoria, and drug preference over monetary incentives. Isradipine lacked any stimulant or abuse liability effects or the propensity to elicit craving, and it did not antagonize any of cocaine's stimulant-related effects associated with its abuse liability. In conclusion, SR Isradipine (up to 30 mg) does not antagonize cocaine's rewarding effects in cocaine-dependent individuals. While higher Isradipine doses may have been more effective at antagonizing cocaine reward, we could not test such doses due to the risk of serious adverse events. Also, Isradipine-mediated inhibition of mesolimbic DA release may be an ineffective treatment of cocaine dependence.
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Effects of Isradipine, a Dihydropyridine-Class Calcium Channel Antagonist, on D-Methamphetamine-Induced Cognitive and Physiological Changes in Humans
Neuropsychopharmacology, 2000Co-Authors: Bankole A. Johnson, Nassima Ait-daoud, Lynda T. WellsAbstract:D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of Isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by Isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.
W Weimar - One of the best experts on this subject based on the ideXlab platform.
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addition of Isradipine lomir results in a better renal function after kidney transplantation a double blind randomized placebo controlled multi center study
Transplantation, 2000Co-Authors: I C Van Riemsdijk, Paul G H Mulder, J W De Fijter, J A Bruijn, J P Van Hooff, A J Hoitsma, Adam Tegzess, W WeimarAbstract:Background. After successful kidney transplantation patients may suffer from the adverse effects due to the use of calcineurin inhibitors. Calcium channel blockers are effective in the treatment of hypertension and may ameliorate cyclosporine- (CsA) induced impairment of renal function after kidney transplantation. Calcium channel blockers may also modulate the immune-system which may result in reduction of acute rejection episodes. Patients and methods. From June 1995 till 1997 the effect of Isradipine (Lomir) on renal function, incidence and severity of delayed graft function (DGF), and acute rejection after kidney transplantation, was studied in 210 renal transplant recipients, who were randomized to receive Isradipine (n=98) or placebo (n=112) after renal transplantation in a double-blind fashion. Results. In the Isradipine group renal function was significantly better at 3 and 12 months (P=0.002 and P=0.021) compared with the placebo group. DGF was present, in both groups: Isradipine: (28+6)/98 (35%); placebo: (35+9)/112 (40%), P=0.57. Severity of DGF was comparable in both groups (Isradipine: 9.1+/-8.7 vs. placebo: 9.3+/-8.1 days). No statistical difference was found in incidence or severity of biopsy-proven acute rejection [Isradipine: (42+6)/98 (49%) versus placebo: (46+9)/112 (49%), P=1.00]. Renal vein thrombosis was observed in eight patients, This proved to be associated with the route of administration of the study medication [6/45 (13%) on i.v. medication versus 2/165 (1%) on oral medication, P Conclusions. Addition of Isradipine results in a better renal function after kidney transplantation, without effect on incidence or severity of DGF or acute rejection.
