{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1222"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1222","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"Discriminative stimulus properties of 3-substituent rimonabant analogs","abstract":"Cannabinoid agonists (e.g., THC) dose-dependently decrease locomotor activity and body temperature and produce antinociception and catalepsy. Drugs that produce this tetrad of effects within a limited dose range are likely to function as CB1 receptor agonists. A structure activity relationship study from our laboratory investigating analogs of the CB1 antagonist rimonabant revealed that certain alterations in the 3-substituent of rimonabant’s pyrazole core conferred agonist-like properties in the tetrad. Interestingly, these effects were present in CB1 -/- mice, and were not reversed by rimonabant in wild-type mice. The present study evaluated two novel 3-substituent rimonabant analogs, O-6629 and O-6658 in the tetrad and drug discrimination, a preclinical model of drug subjective effects that possesses a high degree of pharmacological specificity. Drugs that elicit cannabinergic psychoactive effects in humans are likely to produce THC-like operant responding in animals trained to discriminate between the interoceptive stimuli produced by THC relative to vehicle. O-6629 and O-6658 decreased locomotor activity and body temperature and produced catalepsy. O-6629, but not O-6658 produced significant antinociception. However, these drugs differed from THC in regard to the magnitude of tetrad effects observed. These analogs also failed to elicit THC-like discriminative stimulus effects, nor did they antagonize THC’s discriminative stimulus in mice discriminating 5.6 mg/kg THC from vehicle. Finally, mice were trained to discriminate 5.6 mg/kg O-6629 from vehicle. O-6658 produced full substitution for O-6629, whereas the cannabinoid agonists THC and anandamide did not. O-6629’s discriminative stimulus failed to generalize to rimonabant, cocaine or morphine, whereas WIN 55,212-2 and nicotine evoked partial substitution. These results suggest that these analogs might exert their pharmacological properties through a novel cannabinoid receptor, as has been proposed for WIN 55,212-2 and anandamide. Additionally, O-6629’s discriminative stimulus may involve nicotinic acetylcholine or dopaminergic components. Future directions include determining whether the partial substitution observed with nicotine was mediated through a nicotinic mechanism. Tests with chlorpromazine, an antipsychotic that is a false positive in the tetrad, and diazepam, which produces partial substitution for THC’s discriminative stimulus through a GABAergic mechanism are also planned.","abstract_html":"Cannabinoid agonists (e.g., THC) dose-dependently decrease locomotor activity and body temperature and produce antinociception and catalepsy. Drugs that produce this tetrad of effects within a limited dose range are likely to function as CB1 receptor agonists. A structure activity relationship study from our laboratory investigating analogs of the CB1 antagonist rimonabant revealed that certain alterations in the 3-substituent of rimonabant’s pyrazole core conferred agonist-like properties in the tetrad. Interestingly, these effects were present in CB1 -/- mice, and were not reversed by rimonabant in wild-type mice. The present study evaluated two novel 3-substituent rimonabant analogs, O-6629 and O-6658 in the tetrad and drug discrimination, a preclinical model of drug subjective effects that possesses a high degree of pharmacological specificity. Drugs that elicit cannabinergic psychoactive effects in humans are likely to produce THC-like operant responding in animals trained to discriminate between the interoceptive stimuli produced by THC relative to vehicle. O-6629 and O-6658 decreased locomotor activity and body temperature and produced catalepsy. O-6629, but not O-6658 produced significant antinociception. However, these drugs differed from THC in regard to the magnitude of tetrad effects observed. These analogs also failed to elicit THC-like discriminative stimulus effects, nor did they antagonize THC’s discriminative stimulus in mice discriminating 5.6 mg/kg THC from vehicle. Finally, mice were trained to discriminate 5.6 mg/kg O-6629 from vehicle. O-6658 produced full substitution for O-6629, whereas the cannabinoid agonists THC and anandamide did not. O-6629’s discriminative stimulus failed to generalize to rimonabant, cocaine or morphine, whereas WIN 55,212-2 and nicotine evoked partial substitution. These results suggest that these analogs might exert their pharmacological properties through a novel cannabinoid receptor, as has been proposed for WIN 55,212-2 and anandamide. Additionally, O-6629’s discriminative stimulus may involve nicotinic acetylcholine or dopaminergic components. Future directions include determining whether the partial substitution observed with nicotine was mediated through a nicotinic mechanism. Tests with chlorpromazine, an antipsychotic that is a false positive in the tetrad, and diazepam, which produces partial substitution for THC’s discriminative stimulus through a GABAergic mechanism are also planned.","abstract_has_math":false,"creators":["Walentiny, D. Matthew"],"institution":null,"degree_name":"Doctor of Philosophy","degree_level":"Dissertation","degree_discipline":"Psychology","degree_department":null,"school":null,"contributors":["Jenny Wiley"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-04-29T07:00:00Z","date_published":"2011-04-29T07:00:00Z","updated_at":"2026-07-24T05:53:41Z","subjects":["Rimonabant","Drug discrimination","Psychology","Social and Behavioral Sciences"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/223"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/223","href":"https://scholarscompass.vcu.edu/etd/223","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/M6NV-8E37","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Jenny Wiley"]},{"key":"dc:creator","label":"Author","values":["Walentiny, D. 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Drugs that produce this tetrad of effects within a limited dose range are likely to function as CB1 receptor agonists. A structure activity relationship study from our laboratory investigating analogs of the CB1 antagonist rimonabant revealed that certain alterations in the 3-substituent of rimonabant’s pyrazole core conferred agonist-like properties in the tetrad. Interestingly, these effects were present in CB1 -/- mice, and were not reversed by rimonabant in wild-type mice. The present study evaluated two novel 3-substituent rimonabant analogs, O-6629 and O-6658 in the tetrad and drug discrimination, a preclinical model of drug subjective effects that possesses a high degree of pharmacological specificity. Drugs that elicit cannabinergic psychoactive effects in humans are likely to produce THC-like operant responding in animals trained to discriminate between the interoceptive stimuli produced by THC relative to vehicle. O-6629 and O-6658 decreased locomotor activity and body temperature and produced catalepsy. O-6629, but not O-6658 produced significant antinociception. However, these drugs differed from THC in regard to the magnitude of tetrad effects observed. These analogs also failed to elicit THC-like discriminative stimulus effects, nor did they antagonize THC’s discriminative stimulus in mice discriminating 5.6 mg/kg THC from vehicle. Finally, mice were trained to discriminate 5.6 mg/kg O-6629 from vehicle. O-6658 produced full substitution for O-6629, whereas the cannabinoid agonists THC and anandamide did not. O-6629’s discriminative stimulus failed to generalize to rimonabant, cocaine or morphine, whereas WIN 55,212-2 and nicotine evoked partial substitution. These results suggest that these analogs might exert their pharmacological properties through a novel cannabinoid receptor, as has been proposed for WIN 55,212-2 and anandamide. Additionally, O-6629’s discriminative stimulus may involve nicotinic acetylcholine or dopaminergic components. Future directions include determining whether the partial substitution observed with nicotine was mediated through a nicotinic mechanism. Tests with chlorpromazine, an antipsychotic that is a false positive in the tetrad, and diazepam, which produces partial substitution for THC’s discriminative stimulus through a GABAergic mechanism are also planned."]},{"key":"dc:title","label":"Title","values":["Discriminative stimulus properties of 3-substituent rimonabant analogs"]}]}],"canonical_facts":{"dc:contributor":["Jenny Wiley"],"dc:creator":["Walentiny, D. Matthew"],"dc:date.available":["2016-05-13T07:00:00Z"],"dc:description.abstract":["Cannabinoid agonists (e.g., THC) dose-dependently decrease locomotor activity and body temperature and produce antinociception and catalepsy. Drugs that produce this tetrad of effects within a limited dose range are likely to function as CB1 receptor agonists. A structure activity relationship study from our laboratory investigating analogs of the CB1 antagonist rimonabant revealed that certain alterations in the 3-substituent of rimonabant’s pyrazole core conferred agonist-like properties in the tetrad. Interestingly, these effects were present in CB1 -/- mice, and were not reversed by rimonabant in wild-type mice. The present study evaluated two novel 3-substituent rimonabant analogs, O-6629 and O-6658 in the tetrad and drug discrimination, a preclinical model of drug subjective effects that possesses a high degree of pharmacological specificity. Drugs that elicit cannabinergic psychoactive effects in humans are likely to produce THC-like operant responding in animals trained to discriminate between the interoceptive stimuli produced by THC relative to vehicle. O-6629 and O-6658 decreased locomotor activity and body temperature and produced catalepsy. O-6629, but not O-6658 produced significant antinociception. However, these drugs differed from THC in regard to the magnitude of tetrad effects observed. These analogs also failed to elicit THC-like discriminative stimulus effects, nor did they antagonize THC’s discriminative stimulus in mice discriminating 5.6 mg/kg THC from vehicle. Finally, mice were trained to discriminate 5.6 mg/kg O-6629 from vehicle. O-6658 produced full substitution for O-6629, whereas the cannabinoid agonists THC and anandamide did not. O-6629’s discriminative stimulus failed to generalize to rimonabant, cocaine or morphine, whereas WIN 55,212-2 and nicotine evoked partial substitution. These results suggest that these analogs might exert their pharmacological properties through a novel cannabinoid receptor, as has been proposed for WIN 55,212-2 and anandamide. Additionally, O-6629’s discriminative stimulus may involve nicotinic acetylcholine or dopaminergic components. Future directions include determining whether the partial substitution observed with nicotine was mediated through a nicotinic mechanism. Tests with chlorpromazine, an antipsychotic that is a false positive in the tetrad, and diazepam, which produces partial substitution for THC’s discriminative stimulus through a GABAergic mechanism are also planned."],"dc:identifier":["https://doi.org/10.25772/M6NV-8E37","https://scholarscompass.vcu.edu/etd/223"],"dc:rights":["© The Author"],"dc:subject":["Rimonabant","Drug discrimination","Psychology","Social and Behavioral Sciences"],"dc:title":["Discriminative stimulus properties of 3-substituent rimonabant analogs"],"thesis:degree_discipline":["Psychology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy"]},"updated_at":"2026-07-24T05:53:41Z"}