Igor Krisch - Academia.edu (original) (raw)

Papers by Igor Krisch

Research paper thumbnail of Ergoline derivatives of 1-propinylamine, a process for the manufacture thereof and the use thereof for medicaments

Research paper thumbnail of Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta

Research paper thumbnail of Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

European Journal of Pharmacology, Mar 1, 1999

Ž .

Research paper thumbnail of Loss of endothelium-mediated vascular relaxation as a response to various clamping pressures

The contraction/relaxa- tion responses of thoracic aortal rings clamped with two clamping pressur... more The contraction/relaxa- tion responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning elec- tron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wi- star albino rats, weighing 328 _+ 19

Research paper thumbnail of Structure-activity study of some newly synthesized ergoline derivatives on 5-HT2 receptors and alpha-adrenoceptors in rabbit isolated aorta

Pharmacology, Feb 1, 1992

ABSTRACT

Research paper thumbnail of Ergoline derivatives of 2-propinylamine, a process for the manufacture thereof and the use thereof for medicaments

Research paper thumbnail of Treatment of psychostimulant addiction

Research paper thumbnail of Treatment of Psychostimulant Addiction

Research paper thumbnail of Loss of endothelium mediated vascular relaxation as a response to various clamping pressure: Part I. A pharmacological study

Panminerva medica

The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures... more The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning electron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wistar albino rats, weighing 328 _+ 19 g (mean _+ SD), the thoracic aorta was occluded for 15 rain and then three vascular rings (2 mm wide) were excised. The proximal unclamped ring served as a control. The aorta diameter was calculated from the circumference of distal rings 1.61 +_0.01 mm (n= 15, dmin = 1.51 mm, dm~×= 1.70 ram). The rings were challenged with cumulative additions of KC1 (10-80 mmol/1) to measure the contraction. Then cumulative relaxation on the administration of carbachol (0.01-100 gmol/1) as a response to noradrenaline precontraction (0.1 gmol/1) was determined. A significant loss (P < 0.05) of vascular relaxation in all clamped rings (clamped with Pa and PB clamping pressures) was seen. No significant differences (P > 0.05) were observed for contraction between clamped and control rings clamped with clamp A, however the rings clamped with clamp B showed significantly reduction of contraction (P< 0.05). No significant differences were seen from control rings between groups A and B (P>0.05), as well as from clamped rings between groups A and B (P > 0.05) for both the contraction and relaxation parts of the experiments. With SEM, great endothelial lacerations with complete disruption of the endothelial layer in the rings clamped with the clamp B were seen, but no disruption in rings clamped with clamp A. Therefore endothelial vascular layers are much more susceptible to pressure injuries than was previously believed. The clamped vessel wall injuries, particularly in endothelial layers, depend on the momentary peak clamping pressure (MPCP) as well as on the lower stationary clamping pressure (SCP). [Eur J Cardio-thorac Surg (1996) 10: 684-689]

Research paper thumbnail of Pharmacological studies with two new ergoline derivatives, the potential antipsychotics LEK-8829 and LEK-8841

Journal of Pharmacology and Experimental Therapeutics

The pharmacological properties of 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8 beta-aminomet... more The pharmacological properties of 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8 beta-aminomethylergoline (LEK-8829) and 9,10-didehydro-N-methyl-N-(2-propynyl)-2-bromo-6-methylergoline -8-beta-carboxamide (LEK-8841), new ergoline derivatives, were compared with those of haloperidol and clozapine by in vitro radioligand displacement assays, various behavioral tests and blood pressure measurements. Both ergolines displayed low affinity for rat striatal 3H-SCH23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pin e)- labeled dopamine (D)1 binding sites and high affinity for striatal 3H-spiperone-labeled D2 and cortical 3H-ketanserin-labeled serotonin-2 (5-HT2) sites. The ratio of pKi values 5-HT2/D2 was 1.11 for LEK-8829 (close to that of clozapine, 1.13) and 0.98 for LEK-8841 (close to that of haloperidol, 0.95). All compounds inhibited apomorphine-induced locomotor activity in rats, apomorphine-induced climbing behavior in mice and 5-hydroxytryptophan-induced head twitches in mice and induced catalepsy in rats and in mice. LEK-8829 and clozapine, but not LEK-8841 and haloperidol, showed a certain degree of mesolimbic selectivity, i.e., they caused more potent inhibition of apomorphine-induced locomotion compared with the induction of catalepsy in rats. In the case of LEK-8829, nonspecific effects that presumably predict a side effect profile, such as potentiation of pentobarbital-induced anesthesia in mice (sedation), antagonism of oxotremorine-induced tremors in mice (anticholinergic activity), spontaneous locomotor activity in mice and norepinephrine-induced lethality in rats (sedation and hypotension), were relatively weak compared with the activities described earlier. In contrast, LEK-8841 showed nonspecific effects at the similar dose levels as dopamine and 5-HT antagonistic effects. The results of direct measurements of the influences of both compounds on blood pressure agreed with the previously mentioned findings, i.e., LEK-8829 was relatively less hypotensive than LEK-8841 was. It is suggested that LEK-8829 might be an efficient antipsychotic with a reduced propensity to cause sedative, anticholinergic and hypotensive side effects. A certain degree of mesolimbic selectivity also points toward the possibility of a reduced propensity to cause extrapyramidal symptoms. In contrast, in regard to side effects (including extrapyramidal symptoms), the profile of LEK-8841 is less promising.

Research paper thumbnail of Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam

Journal of Pharmaceutical Sciences, 2015

Research paper thumbnail of Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A receptor agonist and 5-HT2 receptor antagonist activity

Pharmacology Biochemistry and Behavior, 1994

KRISCH, I. AND B. BOLE-VUNDUK. Behavioral studies on LEK-8804, a new ergofine derivative with pot... more KRISCH, I. AND B. BOLE-VUNDUK. Behavioral studies on LEK-8804, a new ergofine derivative with potent 5-HTIA receptor agonist and 5-HT2 receptor antagonist activity. PHARMACOL BIOCHEM BEHAV 47(2) [301][302][303][304][305] 1994.-The 5-HTLA receptor-mediated tall flick response in rats and the 5-HT2 receptor-mediated head twitch response in mice were used to study the functional activity of a new ergoline derivative, 9,10-didehydro-N-(2-propynyl)-6-methylergoline-8/~-carboxamide (LEK-8804). LEK-8804 dose-dependently elicited spontaneous tail flicks in rats, indicating a full 5-hydroxytryptamine~^ (5-HT~,0 agonist activity. This effect was very similar to that produced by the selective 5-HTtA agonist 8-OH-DPAT, both in terms of potency and time-effect relationship, and was blocked by the selective 5-HT~A antagonist . In contrast, LEK-8804 by itself failed to produce head twitches in mice but dose-dependently inhibited the 5-hydroxytryptophan (5-HTP)induced behavior. The inhibitory effect of LEK-S804 upon 5-HTP-induced head twitches was not attenuated by the selective 5-HT~A antagonist . This indicates that probably not the agonist action on 5-HT1A receptors but instead the antagonism on 5-HT2 receptors was involved in the inhibition of head twitch response. It is suggested that LEK-8804 is a potent full 5-HT~A receptor agonist with possible 5-HT2 receptor antagonist properties.

Research paper thumbnail of Structure-Activity Study of Some Newly Synthesized Ergoline Derivatives on 5-HT<sub>2</sub> Receptors and Alpha-Adrenoceptors in Rabbit Isolated Aorta

Pharmacology, 1992

ABSTRACT

Research paper thumbnail of Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta

Pharmacological Research, 1995

Research paper thumbnail of Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

European Journal of Pharmacology, 1999

Ž .

Research paper thumbnail of Loss of endothelium-mediated vascular relaxation as a response to various clamping pressures

European Journal of Cardio-Thoracic Surgery, 1996

The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures... more The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning electron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wistar albino rats, weighing 328 _+ 19 g (mean _+ SD), the thoracic aorta was occluded for 15 rain and then three vascular rings (2 mm wide) were excised. The proximal unclamped ring served as a control. The aorta diameter was calculated from the circumference of distal rings 1.61 +_0.01 mm (n= 15, dmin = 1.51 mm, dm~×= 1.70 ram). The rings were challenged with cumulative additions of KC1 (10-80 mmol/1) to measure the contraction. Then cumulative relaxation on the administration of carbachol (0.01-100 gmol/1) as a response to noradrenaline precontraction (0.1 gmol/1) was determined. A significant loss (P < 0.05) of vascular relaxation in all clamped rings (clamped with Pa and PB clamping pressures) was seen. No significant differences (P > 0.05) were observed for contraction between clamped and control rings clamped with clamp A, however the rings clamped with clamp B showed significantly reduction of contraction (P< 0.05). No significant differences were seen from control rings between groups A and B (P>0.05), as well as from clamped rings between groups A and B (P > 0.05) for both the contraction and relaxation parts of the experiments. With SEM, great endothelial lacerations with complete disruption of the endothelial layer in the rings clamped with the clamp B were seen, but no disruption in rings clamped with clamp A. Therefore endothelial vascular layers are much more susceptible to pressure injuries than was previously believed. The clamped vessel wall injuries, particularly in endothelial layers, depend on the momentary peak clamping pressure (MPCP) as well as on the lower stationary clamping pressure (SCP). [Eur J Cardio-thorac Surg (1996) 10: 684-689]

Research paper thumbnail of A New Ergoline Derivative, LEK-8829, as a Potential New Antipsychotic Drug

Research paper thumbnail of The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats

Naunyn-Schmiedeberg's Archives of Pharmacology, 2004

Various dopaminergic drugs have been studied for their efficacy in the treatment of cocaine addic... more Various dopaminergic drugs have been studied for their efficacy in the treatment of cocaine addiction. Pretreatment with either selective dopamine D 1 receptor agonists or selective dopamine D 2 receptor antagonists prevents reinstatement of cocaine-seeking in animal models of drug craving and relapse. We tested a novel ergoline derivative with combined D 1 agonistic and D 2 antagonistic effects, 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8β-aminomethylergoline bimaleate (LEK-8829), for its effects on cocaine-seeking in the intravenous cocaine selfadministration model in rats. Pretreatment with systemic injections of LEK-8829 attenuated reinstatement of cocaineseeking induced by cocaine priming injections and diminished cocaine intake in cocaine self-administration sessions. LEK-8829 itself did not induce reinstatement of cocaine-seeking and did not maintain intravenous self-administration. The results of our study indicate that LEK-8829 is a candidate medication for the treatment of cocaine craving in cocaine addiction.

Research paper thumbnail of Ergoline derivatives of 1-propinylamine, a process for the manufacture thereof and the use thereof for medicaments

Research paper thumbnail of Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta

Research paper thumbnail of Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

European Journal of Pharmacology, Mar 1, 1999

Ž .

Research paper thumbnail of Loss of endothelium-mediated vascular relaxation as a response to various clamping pressures

The contraction/relaxa- tion responses of thoracic aortal rings clamped with two clamping pressur... more The contraction/relaxa- tion responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning elec- tron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wi- star albino rats, weighing 328 _+ 19

Research paper thumbnail of Structure-activity study of some newly synthesized ergoline derivatives on 5-HT2 receptors and alpha-adrenoceptors in rabbit isolated aorta

Pharmacology, Feb 1, 1992

ABSTRACT

Research paper thumbnail of Ergoline derivatives of 2-propinylamine, a process for the manufacture thereof and the use thereof for medicaments

Research paper thumbnail of Treatment of psychostimulant addiction

Research paper thumbnail of Treatment of Psychostimulant Addiction

Research paper thumbnail of Loss of endothelium mediated vascular relaxation as a response to various clamping pressure: Part I. A pharmacological study

Panminerva medica

The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures... more The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning electron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wistar albino rats, weighing 328 _+ 19 g (mean _+ SD), the thoracic aorta was occluded for 15 rain and then three vascular rings (2 mm wide) were excised. The proximal unclamped ring served as a control. The aorta diameter was calculated from the circumference of distal rings 1.61 +_0.01 mm (n= 15, dmin = 1.51 mm, dm~×= 1.70 ram). The rings were challenged with cumulative additions of KC1 (10-80 mmol/1) to measure the contraction. Then cumulative relaxation on the administration of carbachol (0.01-100 gmol/1) as a response to noradrenaline precontraction (0.1 gmol/1) was determined. A significant loss (P < 0.05) of vascular relaxation in all clamped rings (clamped with Pa and PB clamping pressures) was seen. No significant differences (P > 0.05) were observed for contraction between clamped and control rings clamped with clamp A, however the rings clamped with clamp B showed significantly reduction of contraction (P< 0.05). No significant differences were seen from control rings between groups A and B (P>0.05), as well as from clamped rings between groups A and B (P > 0.05) for both the contraction and relaxation parts of the experiments. With SEM, great endothelial lacerations with complete disruption of the endothelial layer in the rings clamped with the clamp B were seen, but no disruption in rings clamped with clamp A. Therefore endothelial vascular layers are much more susceptible to pressure injuries than was previously believed. The clamped vessel wall injuries, particularly in endothelial layers, depend on the momentary peak clamping pressure (MPCP) as well as on the lower stationary clamping pressure (SCP). [Eur J Cardio-thorac Surg (1996) 10: 684-689]

Research paper thumbnail of Pharmacological studies with two new ergoline derivatives, the potential antipsychotics LEK-8829 and LEK-8841

Journal of Pharmacology and Experimental Therapeutics

The pharmacological properties of 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8 beta-aminomet... more The pharmacological properties of 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8 beta-aminomethylergoline (LEK-8829) and 9,10-didehydro-N-methyl-N-(2-propynyl)-2-bromo-6-methylergoline -8-beta-carboxamide (LEK-8841), new ergoline derivatives, were compared with those of haloperidol and clozapine by in vitro radioligand displacement assays, various behavioral tests and blood pressure measurements. Both ergolines displayed low affinity for rat striatal 3H-SCH23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaze pin e)- labeled dopamine (D)1 binding sites and high affinity for striatal 3H-spiperone-labeled D2 and cortical 3H-ketanserin-labeled serotonin-2 (5-HT2) sites. The ratio of pKi values 5-HT2/D2 was 1.11 for LEK-8829 (close to that of clozapine, 1.13) and 0.98 for LEK-8841 (close to that of haloperidol, 0.95). All compounds inhibited apomorphine-induced locomotor activity in rats, apomorphine-induced climbing behavior in mice and 5-hydroxytryptophan-induced head twitches in mice and induced catalepsy in rats and in mice. LEK-8829 and clozapine, but not LEK-8841 and haloperidol, showed a certain degree of mesolimbic selectivity, i.e., they caused more potent inhibition of apomorphine-induced locomotion compared with the induction of catalepsy in rats. In the case of LEK-8829, nonspecific effects that presumably predict a side effect profile, such as potentiation of pentobarbital-induced anesthesia in mice (sedation), antagonism of oxotremorine-induced tremors in mice (anticholinergic activity), spontaneous locomotor activity in mice and norepinephrine-induced lethality in rats (sedation and hypotension), were relatively weak compared with the activities described earlier. In contrast, LEK-8841 showed nonspecific effects at the similar dose levels as dopamine and 5-HT antagonistic effects. The results of direct measurements of the influences of both compounds on blood pressure agreed with the previously mentioned findings, i.e., LEK-8829 was relatively less hypotensive than LEK-8841 was. It is suggested that LEK-8829 might be an efficient antipsychotic with a reduced propensity to cause sedative, anticholinergic and hypotensive side effects. A certain degree of mesolimbic selectivity also points toward the possibility of a reduced propensity to cause extrapyramidal symptoms. In contrast, in regard to side effects (including extrapyramidal symptoms), the profile of LEK-8841 is less promising.

Research paper thumbnail of Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Levetiracetam

Journal of Pharmaceutical Sciences, 2015

Research paper thumbnail of Behavioral studies on LEK-8804, a new ergoline derivative with potent 5-HT1A receptor agonist and 5-HT2 receptor antagonist activity

Pharmacology Biochemistry and Behavior, 1994

KRISCH, I. AND B. BOLE-VUNDUK. Behavioral studies on LEK-8804, a new ergofine derivative with pot... more KRISCH, I. AND B. BOLE-VUNDUK. Behavioral studies on LEK-8804, a new ergofine derivative with potent 5-HTIA receptor agonist and 5-HT2 receptor antagonist activity. PHARMACOL BIOCHEM BEHAV 47(2) [301][302][303][304][305] 1994.-The 5-HTLA receptor-mediated tall flick response in rats and the 5-HT2 receptor-mediated head twitch response in mice were used to study the functional activity of a new ergoline derivative, 9,10-didehydro-N-(2-propynyl)-6-methylergoline-8/~-carboxamide (LEK-8804). LEK-8804 dose-dependently elicited spontaneous tail flicks in rats, indicating a full 5-hydroxytryptamine~^ (5-HT~,0 agonist activity. This effect was very similar to that produced by the selective 5-HTtA agonist 8-OH-DPAT, both in terms of potency and time-effect relationship, and was blocked by the selective 5-HT~A antagonist . In contrast, LEK-8804 by itself failed to produce head twitches in mice but dose-dependently inhibited the 5-hydroxytryptophan (5-HTP)induced behavior. The inhibitory effect of LEK-S804 upon 5-HTP-induced head twitches was not attenuated by the selective 5-HT~A antagonist . This indicates that probably not the agonist action on 5-HT1A receptors but instead the antagonism on 5-HT2 receptors was involved in the inhibition of head twitch response. It is suggested that LEK-8804 is a potent full 5-HT~A receptor agonist with possible 5-HT2 receptor antagonist properties.

Research paper thumbnail of Structure-Activity Study of Some Newly Synthesized Ergoline Derivatives on 5-HT<sub>2</sub> Receptors and Alpha-Adrenoceptors in Rabbit Isolated Aorta

Pharmacology, 1992

ABSTRACT

Research paper thumbnail of Comparative 5-HT2A-receptor and alpha1-adrenoceptor antagonistic activity of an ergoline LEK-8829 and its degradation product LEK-1814 in rabbit isolated aorta

Pharmacological Research, 1995

Research paper thumbnail of Stereoselective and endothelium-independent action of nicardipine on the isolated porcine coronary artery

European Journal of Pharmacology, 1999

Ž .

Research paper thumbnail of Loss of endothelium-mediated vascular relaxation as a response to various clamping pressures

European Journal of Cardio-Thoracic Surgery, 1996

The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures... more The contraction/relaxation responses of thoracic aortal rings clamped with two clamping pressures to potassium chloride (KC1), noradrenaline and carbachol were studied using a scanning electron microscope (SEM) to ascertain endothelial lacerations. Clamp A had the tip pressure PA = 0.60 N/ram 2 and clamp B PB=5.16 N/mm 2. In 15 Wistar albino rats, weighing 328 _+ 19 g (mean _+ SD), the thoracic aorta was occluded for 15 rain and then three vascular rings (2 mm wide) were excised. The proximal unclamped ring served as a control. The aorta diameter was calculated from the circumference of distal rings 1.61 +_0.01 mm (n= 15, dmin = 1.51 mm, dm~×= 1.70 ram). The rings were challenged with cumulative additions of KC1 (10-80 mmol/1) to measure the contraction. Then cumulative relaxation on the administration of carbachol (0.01-100 gmol/1) as a response to noradrenaline precontraction (0.1 gmol/1) was determined. A significant loss (P < 0.05) of vascular relaxation in all clamped rings (clamped with Pa and PB clamping pressures) was seen. No significant differences (P > 0.05) were observed for contraction between clamped and control rings clamped with clamp A, however the rings clamped with clamp B showed significantly reduction of contraction (P< 0.05). No significant differences were seen from control rings between groups A and B (P>0.05), as well as from clamped rings between groups A and B (P > 0.05) for both the contraction and relaxation parts of the experiments. With SEM, great endothelial lacerations with complete disruption of the endothelial layer in the rings clamped with the clamp B were seen, but no disruption in rings clamped with clamp A. Therefore endothelial vascular layers are much more susceptible to pressure injuries than was previously believed. The clamped vessel wall injuries, particularly in endothelial layers, depend on the momentary peak clamping pressure (MPCP) as well as on the lower stationary clamping pressure (SCP). [Eur J Cardio-thorac Surg (1996) 10: 684-689]

Research paper thumbnail of A New Ergoline Derivative, LEK-8829, as a Potential New Antipsychotic Drug

Research paper thumbnail of The dopamine D1 receptor agonist and D2 receptor antagonist LEK-8829 attenuates reinstatement of cocaine-seeking in rats

Naunyn-Schmiedeberg's Archives of Pharmacology, 2004

Various dopaminergic drugs have been studied for their efficacy in the treatment of cocaine addic... more Various dopaminergic drugs have been studied for their efficacy in the treatment of cocaine addiction. Pretreatment with either selective dopamine D 1 receptor agonists or selective dopamine D 2 receptor antagonists prevents reinstatement of cocaine-seeking in animal models of drug craving and relapse. We tested a novel ergoline derivative with combined D 1 agonistic and D 2 antagonistic effects, 9,10-didehydro-N-methyl-N-(2-propynyl)-6-methyl-8β-aminomethylergoline bimaleate (LEK-8829), for its effects on cocaine-seeking in the intravenous cocaine selfadministration model in rats. Pretreatment with systemic injections of LEK-8829 attenuated reinstatement of cocaineseeking induced by cocaine priming injections and diminished cocaine intake in cocaine self-administration sessions. LEK-8829 itself did not induce reinstatement of cocaine-seeking and did not maintain intravenous self-administration. The results of our study indicate that LEK-8829 is a candidate medication for the treatment of cocaine craving in cocaine addiction.