ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01611.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb02069.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00692.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb02070.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractThe receptor pharmacology of amperozide was investigated with in vitro radioligand binding technique. Amperozide possessed a high affinity to the 5‐HT2receptors (Ki= 16.5±2.1 nM) and a moderate affinity to α1‐adrenergic receptors of rat cerebral cortical membranes (Ki=172±14 nM). The affinity of amperozide for striatal and limbic dopamine D2receptors was low and not significantly different (Ki±S.E.M. = 540 ± 59 nM vs 403±42 nM; p<0.11, n = 4). The affinity for striatal and limbic 5‐HT2receptors was measured as well and found to be very close to the affinity to the cerebral cortical 5‐HT2receptor. The drug affinity for D2and 5‐HT2receptors seems thus not to be influenced by the location of the receptor moiety. The affinity for several other rat brain receptors such as 5‐HT1A, α2‐adrenergic, dopamine D1muscarinic M1 and M2, opiate sigma and β2‐adrenergic was low.The pseudo‐Hill coefficient of the amperozide competition binding curve was consistently higher than one indicating antagonistic and complex interactions with the 5‐HT2receptor or with α1‐adrenergic and dopamine D2receptors.The antagonistic properties of amperozide were investigated by its ability to antagonize the serotonin‐induced formation of inositol‐1‐phosphate in human blood platelets. Amperozide inhibited this 5‐HT2receptor‐mediated intracellular response with similar potency as ketanserin.These results suggest that amperozide

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01599.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb00693.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractAmperozide, a new putatively antipsychotic drug, was found to exert a functional selectivity for the limbic system of the brain. Thus, amperozide was as active as both classical and atypical neuroleptics on hypermotility induced by a low dose of amphetamine. On the other hand, amperozide did not produce catalepsy, nor did it reverse amphetamine‐induced stereotypies. Moreover, amperozide inhibited exploratory behaviour in mice. The present results indicate an antipsychotic effect of amperozide, with a minimal risk for EPS when used in the clini

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01600.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb02071.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractAmperozide, a new putatively antipsychotic compound, has been evaluated for its effect on conditioned avoidance response and food‐reinforced lever‐pressing. Given alone, amperozide was almost equipotent to clozapine, but less potent than haloperidol in both test models. It was found that there was a statistically significant synergism, in these two models, between amperozide and classical neuroleptics. Since amperozide is inactive in behavioural tests reflecting striatal dopaminergic mechanisms, the synergistic effect could be of great therapeutic value in the treatment of psychotic disord

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01601.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

AbstractThe effect of amperozide on DA synapses was studied in 6‐OHDA lesioned rats exhibiting a specific turning behaviour in response to the DA agonists apomorphine and pergolide or indirectly acting stimulating agents like amphetamine. Amperozide, unlike classical neuroleptics, failed to antagonize apomorphine induced turning behaviour in a regular fashion, but showed pergolide antagonism within the D2 receptor selective dose range, suggesting a type of selective interference with dopaminergic nerve transmission which differs from that caused by classical neuroleptics. Furthermore, amperozide antagonized the turning behaviour induced by amphetamine, presumably by interfering with the availability of newly synthesized DA and NA suggesting a similar influence also on other DA releasing agents. Although amperozide potentiated the effects of α‐MPT, the drug seemed not to influence the reserpine sensitive pool o

ISSN:0901-9928    

DOI:10.1111/j.1600-0773.1990.tb01602.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY