Remoxipride, a new selective D2 antagonist, and haloperidol in cebus monkeys

Extrapyramidal Syndromes and New Antipsychotic Drugs: Findings in Patients and Non-human Primate Models

“…The D 2 selective substituted benzamides remoxipride and sulpiride are important agents because they show a wide separation between antagonising stimulant-induced hyperactivity and stereotypical behaviour in rodents (Ogren et ai, 1984). There is a similar separation in the dystonia-inducing and antipsychotic dose-response curves with remoxipride in non-human primates, although the separation in primates is not as wide as that seen in rodents (Gerlach & Casey, 1990). These findings are consistent with clinical investigations showing antipsychotic efficacy at doses that cause relatively low rates of EPS (Lewander et ai, 1990).…”

“…However, the substituted benzamides, such as remoxipride and sulpiride, are intriguing compounds because they are highly selective D 2 antagonists, but produce fewer EPS than would be predicted from a unidimensional model of D 2 antagonism as the sole mechanism of EPS. In contrast to the hypothesised high rates of EPS, these drugs have been associated with relatively few EPS in the clinical setting at effective antipsychotic doses (Lewander et ai, 1990), as well as having a low rate of EPS in non-human primates (Gerlach & Casey, 1990;Casey, 1989aCasey, , 1993b. As yet, there are no good explanations as to why these selective substituted benzamides have a low liability to cause EPS, although either a site selectivity, with preferential action at limbic rather than striatal dopamine sites, or lower D 2 receptor affinity, may be alternative mechanisms of action.…”

Extrapyramidal Syndromes and New Antipsychotic Drugs: Findings in Patients and Non-human Primate Models

“…The D 2 selective substituted benzamides remoxipride and sulpiride are important agents because they show a wide separation between antagonising stimulant-induced hyperactivity and stereotypical behaviour in rodents (Ogren et ai, 1984). There is a similar separation in the dystonia-inducing and antipsychotic dose-response curves with remoxipride in non-human primates, although the separation in primates is not as wide as that seen in rodents (Gerlach & Casey, 1990). These findings are consistent with clinical investigations showing antipsychotic efficacy at doses that cause relatively low rates of EPS (Lewander et ai, 1990).…”

“…However, the substituted benzamides, such as remoxipride and sulpiride, are intriguing compounds because they are highly selective D 2 antagonists, but produce fewer EPS than would be predicted from a unidimensional model of D 2 antagonism as the sole mechanism of EPS. In contrast to the hypothesised high rates of EPS, these drugs have been associated with relatively few EPS in the clinical setting at effective antipsychotic doses (Lewander et ai, 1990), as well as having a low rate of EPS in non-human primates (Gerlach & Casey, 1990;Casey, 1989aCasey, , 1993b. As yet, there are no good explanations as to why these selective substituted benzamides have a low liability to cause EPS, although either a site selectivity, with preferential action at limbic rather than striatal dopamine sites, or lower D 2 receptor affinity, may be alternative mechanisms of action.…”

The Acetylcholinesterase Inhibitor Galantamine Inhibits d-Amphetamine-Induced Psychotic-Like Behavior in Cebus Monkeys

“…The side effect profile of galantamine was also investigated. Several studies from our research laboratory have shown that drugs with antipsychotic activity antagonize d-amphetamine behaviors in Cebus monkeys (Gerlach and Casey, 1990;Andersen et al, 2003;Brandt-Christensen et al, 2006). The monkeys are sensitized to EPS by previous long-term treatment with classical dopamine D 2 antagonists; the EPS observed in these monkeys are very similar to EPS induced by antipsychotic agents in humans, and the model is predictive of EPS liability in the clinic (Peacock and Gerlach, 1993).…”

Time Distortions in Mind

“…The dopamine antagonists, haloperidol, and remoxipride act differentially on these dopamine neural pathways and block the dopamine D2 receptor (DRD2). Initial experiments showed halopiridol affects all the dopamine pathways (Lidow and Goldmanrakic, 1994), while remoxipride leaves the nigrostriatal circuit unblocked (Gerlach and Casey, 1990). Rammsayer and colleagues took advantage of this differential blocking in experiments with humans that implicate the nigrostriatal pathway in timing intervals of less than 500ms and the mesocortical and mesolimbic pathways in timing longer intervals.…”

Extrapyramidal Syndromes and New Antipsychotic Drugs: Findings in Patients and Non-human Primate Models

“…The D 2 selective substituted benzamides remoxipride and sulpiride are important agents because they show a wide separation between antagonising stimulant-induced hyperactivity and stereotypical behaviour in rodents (Ogren et ai, 1984). There is a similar separation in the dystonia-inducing and antipsychotic dose-response curves with remoxipride in non-human primates, although the separation in primates is not as wide as that seen in rodents (Gerlach & Casey, 1990). These findings are consistent with clinical investigations showing antipsychotic efficacy at doses that cause relatively low rates of EPS (Lewander et ai, 1990).…”

“…However, the substituted benzamides, such as remoxipride and sulpiride, are intriguing compounds because they are highly selective D 2 antagonists, but produce fewer EPS than would be predicted from a unidimensional model of D 2 antagonism as the sole mechanism of EPS. In contrast to the hypothesised high rates of EPS, these drugs have been associated with relatively few EPS in the clinical setting at effective antipsychotic doses (Lewander et ai, 1990), as well as having a low rate of EPS in non-human primates (Gerlach & Casey, 1990;Casey, 1989aCasey, , 1993b. As yet, there are no good explanations as to why these selective substituted benzamides have a low liability to cause EPS, although either a site selectivity, with preferential action at limbic rather than striatal dopamine sites, or lower D 2 receptor affinity, may be alternative mechanisms of action.…”

The Acetylcholinesterase Inhibitor Galantamine Inhibits d-Amphetamine-Induced Psychotic-Like Behavior in Cebus Monkeys

“…The side effect profile of galantamine was also investigated. Several studies from our research laboratory have shown that drugs with antipsychotic activity antagonize d-amphetamine behaviors in Cebus monkeys (Gerlach and Casey, 1990;Andersen et al, 2003;Brandt-Christensen et al, 2006). The monkeys are sensitized to EPS by previous long-term treatment with classical dopamine D 2 antagonists; the EPS observed in these monkeys are very similar to EPS induced by antipsychotic agents in humans, and the model is predictive of EPS liability in the clinic (Peacock and Gerlach, 1993).…”

Time Distortions in Mind

“…The dopamine antagonists, haloperidol, and remoxipride act differentially on these dopamine neural pathways and block the dopamine D2 receptor (DRD2). Initial experiments showed halopiridol affects all the dopamine pathways (Lidow and Goldmanrakic, 1994), while remoxipride leaves the nigrostriatal circuit unblocked (Gerlach and Casey, 1990). Rammsayer and colleagues took advantage of this differential blocking in experiments with humans that implicate the nigrostriatal pathway in timing intervals of less than 500ms and the mesocortical and mesolimbic pathways in timing longer intervals.…”

Extrapyramidal Syndromes and New Antipsychotic Drugs: Findings in Patients and Non-human Primate Models

“…The D 2 selective substituted benzamides remoxipride and sulpiride are important agents because they show a wide separation between antagonising stimulant-induced hyperactivity and stereotypical behaviour in rodents (Ogren et ai, 1984). There is a similar separation in the dystonia-inducing and antipsychotic dose-response curves with remoxipride in non-human primates, although the separation in primates is not as wide as that seen in rodents (Gerlach & Casey, 1990). These findings are consistent with clinical investigations showing antipsychotic efficacy at doses that cause relatively low rates of EPS (Lewander et ai, 1990).…”

“…However, the substituted benzamides, such as remoxipride and sulpiride, are intriguing compounds because they are highly selective D 2 antagonists, but produce fewer EPS than would be predicted from a unidimensional model of D 2 antagonism as the sole mechanism of EPS. In contrast to the hypothesised high rates of EPS, these drugs have been associated with relatively few EPS in the clinical setting at effective antipsychotic doses (Lewander et ai, 1990), as well as having a low rate of EPS in non-human primates (Gerlach & Casey, 1990;Casey, 1989aCasey, , 1993b. As yet, there are no good explanations as to why these selective substituted benzamides have a low liability to cause EPS, although either a site selectivity, with preferential action at limbic rather than striatal dopamine sites, or lower D 2 receptor affinity, may be alternative mechanisms of action.…”

The Acetylcholinesterase Inhibitor Galantamine Inhibits d-Amphetamine-Induced Psychotic-Like Behavior in Cebus Monkeys

“…The side effect profile of galantamine was also investigated. Several studies from our research laboratory have shown that drugs with antipsychotic activity antagonize d-amphetamine behaviors in Cebus monkeys (Gerlach and Casey, 1990;Andersen et al, 2003;Brandt-Christensen et al, 2006). The monkeys are sensitized to EPS by previous long-term treatment with classical dopamine D 2 antagonists; the EPS observed in these monkeys are very similar to EPS induced by antipsychotic agents in humans, and the model is predictive of EPS liability in the clinic (Peacock and Gerlach, 1993).…”

Time Distortions in Mind

“…The dopamine antagonists, haloperidol, and remoxipride act differentially on these dopamine neural pathways and block the dopamine D2 receptor (DRD2). Initial experiments showed halopiridol affects all the dopamine pathways (Lidow and Goldmanrakic, 1994), while remoxipride leaves the nigrostriatal circuit unblocked (Gerlach and Casey, 1990). Rammsayer and colleagues took advantage of this differential blocking in experiments with humans that implicate the nigrostriatal pathway in timing intervals of less than 500ms and the mesocortical and mesolimbic pathways in timing longer intervals.…”