Synthesis and dopaminergic activity of 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide

3-(3,4-Dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide was synthesized by a six-step reaction sequence and was evaluated, and compared with apomorphine, for central dopaminergic agonist activity. The compound produced behavioral and biochemical changes characteristic of central dopaminergic stimulation. Administration of 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide to rats resulted in the reversal of the reserpine syndrome, stereotypic behavior, contralateral turning following 6-hydroxydopamine lesion of the substantia nigra, a decrease in dopamine turnover, and inhibition of prolactin release. These results indicate that 3-(3,4-dihydroxyphenyl)-1-n-propylpyrrolidine hydrobromide is a dopaminergic agonist. However, the compound exhibited a lower potency but a slightly longer duration of action than apomorphine.     

Sex differences in the effects of 1-(m-trifluoromethylphenyl) piperazine and 1-(m-chlorophenyl) piperazine on copulatory behavior in the rat

Peripheral administrations of TFMPP (0.2- 1 mg/kg) or MCPP (1 mg/kg) facilitated lordosis behavior in female rats treated with estradiol benzoate, and had no effects in females primed with estradiol benzoate and progesterone. In contrast, TFMPP (1 mg/kg) and MCPP (1 mg/kg) inhibited copulatory behavior in male rats. It is concluded that there are sex differences in the effects of TFMPP and MCPP on copulatory behavior in the rat. Moreover, it is suggested that the effects of these drugs on copulatory behavior may be mediated by activation of 5-HT1B and/or 5-HT1C receptors, or by blockade of activity at 5-HT3 receptors.     

用HPLC法测定丹参素棕榈醇酯脂质体药物含量

目的 建立HPLC法测定丹参素棕榈醇酯脂质体中药物含量的方法。方法 采用Agilent ZORBAX Eclipse Plus C₁₈柱（4.6 mm×200 mm,5 μm）;以乙腈-水（50∶50）含0.02%甲酸和0.02%三乙胺水、以pH 6~7的溶液为流动相,流速为1 ml/min,检测波长为280 nm,柱温为室温。结果 本色谱条件下丹参素棕榈醇酯与辅料及溶剂分离度符合要求,在0.05~0.45 mg/ml范围内线性关系良好（r=0.999 5,n=5）,回收率在96%~102%之间,日内及日间RSD均小于2%（n=5）。3批样品的含量分别为97.81%、101.20%、98.53%。结论 该方法准确可靠、简单快速,可用于丹参素棕榈醇酯脂质体含量的测定。     

β-(3,4-二羟基苯基)-α-羟基丙酸异丙酯滴丸制剂处方优化

目的:优化β-(3,4-二羟基苯基)-α-羟基丙酸异丙酯(IDHP)滴丸的制剂处方。方法:采用Box-Behnken中心组合设计,以载药量、淀粉用量和羧甲基淀粉钠用量为自变量,总评归一化值(OD)为因变量,利用响应曲面法分析自变量对因变量的影响,确定滴丸剂较优处方并进行验证。结果:IDHP滴丸的最佳处方为:载药量为23.0%,淀粉用量为14.0%,CMS-Na用量为4.0%,PEG 6000用量为59.0%。结论:试验所得处方合理,IDHP滴丸的成型质量良好。     

1—（2—吡啶基）哌嗪的合成

用工业品2－氨基吡啶在Br2-HBr体系中重氮化,制得2－溴吡啶,收率73．5％;2－溴吡啶与工业无水哌秦直接反应,制得1－（2－吡啶基）哌嗪,收率60％。     

The selective sigma(1) receptor agonist, 1-(3,4-dimethoxyphenethyl)-4-(phenylpropyl)piperazine (SA4503), blocks the acquisition of the conditioned place preference response to (-)-nicotine in rats

Human immunodeficiency virus (HIV) infection is associated with a progressive dementia, in addition to motor and behavioural deficits. Cognitive deterioration and motor impairments have been observed also in simian immunodeficiency virus (SIV)-infected monkeys, an animal model for HIV infection. We found recently that choline acetyltransferase activity is markedly reduced in brains of SIV-infected monkeys. We report now that selegiline, completely restores the reduced choline acetyltransferase activity which encourages for a meaningful anti-dementia therapeutic strategy.     

Conformational analogues of dopamine. Synthesis and pharmacological activity of (E)- and (Z)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides.

(E)- and (Z)-(+/-)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides were synthesized as part of a program to assess the importance of conformational isomerism with respect to the various peripheral biological actions of dopamine. Although neither of the compounds possessed dopaminergic activity in the canine renal blood-flow model, both agents were weak alpha-adrenergic agonists and exhibited cardiostimulatory properties similar to dopamine. The E isomer was apprxoximately 5 times more potent than the Z isomer in its alpha-adrenergic activity and approximately 15 times as potent in its cardiac effects. Possible reasons for the lack of renal dopaminergic activity exhibited by the E isomer are presented.     

Antagonist properties of 1-(2-pyrimidinyl)piperazine at presynaptic alpha 2-adrenoceptors in the rat brain

The effect of 1-(2-pyrimidinyl)piperazine (PmP), the main metabolite of buspirone, was tested on K(+)-evoked [3H]noradrenaline and [3H]serotonin release from superfused synaptosomes obtained from rat cerebral cortex. PmP had no effects per se, but antagonized the effect of noradrenaline, producing a parallel shift to the right of the noradrenaline inhibition curves. From these data pA2 (apparent affinity) values of 6.8 and 7.3 were calculated for PmP on presynaptic alpha 2-adrenoceptors located on noradrenergic and serotonergic nerve terminals, respectively.     

Enantiomers of 3-(3,4-dihydroxyphenyl)- and 3-(3-hydroxyphenyl)-N-n-propylpiperidine: central pre- and postsynaptic dopaminergic effects and pharmacokinetics

This study emphasizes the importance of the metabolic conversion of the enantiomers of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) into their catechol analogues, the enantiomers of 3-(3,4-dihydroxyphenyl)-N-n-propylpiperidine. These isomers are both shown to be excellent substrates for COMT, with a slight preference for the S-(-) enantiomer. Assessment of the dopaminergic activity of these catechols and the results from the determination of brain levels of the enantiomers of 3-PPP and their metabolites indicate that the metabolites probably do not alter the pharmacological profiles established for (R)-(+)- and (S)-(-)-3-PPP. The conversion of the monophenols into catecholic metabolites is only 1-5%, and the further conversion of these catecholic metabolites into methoxylated analogues is very rapid. However, the very interesting observation was made that, when inhibiting COMT by means of tropolone and subsequently treating the rats with high doses of (S)-(-)-3-PPP (ip), postsynaptic dopaminergic activity was elicited. This has never been seen for (S)-(-)-3-PPP without tropolone pretreatment and might indicate that, in this special case, the catecholic metabolite affects the in vivo pharmacological profile of (S)-(-)-3-PPP.     

Psychopharmacological profile of 1-(m-(trifluoromethyl) phenyl) piperazine (TFMPP)

The effect of TFMPP, an agonist of the 5-HT1b receptors, was studied in mice on several psychopharmacological parameters. In contrast to imipramine-like drugs, TFMPP neither antagonized reserpine-induced hypothermia nor increased yohimbine-induced toxicity. Similarly to imipramine-like drugs, TFMPP antagonized oxotremorine-induced hypothermia and was active in the behavioural despair test. In addition, TFMPP normalized a social behavioural deficit induced by isolation. The effects of TFMPP on oxotremorine-induced hypothermia in the behavioural despair test and in the isolation-induced social behavioural deficit are all antagonized by d-1 propranolol. It is concluded that TFMPP seems to possess psychotropic activity resembling only in part that of imipramine-like drugs and that these actions may be mediated through 5-HT1b receptors.