Assuntos
Antipsicóticos/farmacologia , Dopamina/fisiologia , Receptores de Serotonina/fisiologia , Clozapina/farmacologia , Tratos Extrapiramidais/efeitos dos fármacos , Tratos Extrapiramidais/fisiologia , Humanos , Receptores de Serotonina/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologiaRESUMO
The binding of [3H]-nemonapride to human peripheral blood lymphocytes (PBL) was studied using various competing ligands specific for D2-like dopamine receptors. There is no detectable stereoselectivity for the stereoisomers of butaclamol, and competitions with haloperidol and sulpiride also show no evidence of specific binding to D2-like dopamine receptors. RT-PCR of RNA from human lymphocytes showed that there is no detectable D2 mRNA (even with nested PCR). D3 mRNA was, however, detectable by RT-PCR, but only at low levels that could not be detected by Northern blots of PBL total RNA.
Assuntos
Linfócitos/química , Receptores de Dopamina D2/análise , Adulto , Antipsicóticos/farmacocinética , Benzamidas/farmacocinética , Ligação Competitiva , Antagonistas de Dopamina/farmacocinética , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Ensaio Radioligante , Receptores de Dopamina D2/genética , Receptores de Dopamina D3 , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológicoRESUMO
[3H]Nemonapride and [3H]spiperone are very widely used to study dopaminergic systems in vitro and in vivo, but it has been reported that [3H]nemonapride and [3H]spiperone give markedly different Bmax values for preparations of D2 dopamine receptors from recombinant cell lines or animal tissues. We have used the two radioligands in parallel to study a range of dopamine receptors [D2(short), D2(long), and D3] in different buffers. Bmax values derived using either radioligand differ by an average of < 20%, independent of receptor type or buffer conditions. All competition experiments show that the two ligands compete at a single site. It seems that [3H]spiperone and [3H]nemonapride do not differentiate between different forms or populations of D2-like receptors.
Assuntos
Benzamidas/metabolismo , Receptores de Dopamina D2/metabolismo , Receptores Dopaminérgicos/metabolismo , Espiperona/metabolismo , Animais , Sítios de Ligação , Ligação Competitiva , Células CHO , Cricetinae , Antagonistas de Dopamina/metabolismo , Ratos , Receptores de Dopamina D3 , Recombinação Genética , TrítioAssuntos
Benzamidas/metabolismo , Antagonistas de Dopamina/metabolismo , Receptores de Dopamina D2/metabolismo , Espiperona/metabolismo , Animais , Ligação Competitiva , Butaclamol/farmacologia , Células CHO , Cricetinae , Cinética , Ensaio Radioligante , Ratos , Proteínas Recombinantes/metabolismo , Transfecção , TrítioRESUMO
The calcium antagonist nimodipine blocks the effects of many vasoconstrictors of cerebrovascular smooth muscle and may reduce the incidence of delayed cerebral ischaemia following subarachnoid haemorrhage though not necessarily by inhibiting the development of angiographic cerebral vasospasm. Post-haemorrhagic CSF contains abnormally large quantities of various eicosanoids that partly reflect enhanced production by cerebral arteries. Does nimodipine affect this process? The extra-arterial and intra-arterial production of PG6 keto-F1 alpha, PGE2, PGF2 alpha and TXB2 were measured in perfused common carotid arteries taken from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days. All rabbits were given the antifibrinolytic agent tranexamic acid to retard resolution of the clot, and half were given oral nimodipine (2 mg/kg/day) for 10 days. Nimodipine significantly reduced the extra-arterial production of TXB2 during the third and fourth hours of perfusion and, less consistently, the production of PGF2 alpha, PGE2 and PG6 keto-F1 alpha. Lutrol, the solvent for nimodipine, had no such effect.
