Perlapine
(Synonyms: MP-11) 目录号 : GC44601
An atypical neuroleptic
Cas No.:1977-11-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Perlapine is an atypical neuroleptic that blocks dopamine and serotonin (5-HT) receptors (Kis = 60, 30, and 30 nM for D2, D4, and 5-HT2A, respectively). Perlapine is also an agonist for hM3Dq, a designer receptor exclusively activated by designer drugs (DREADDs) derived from the human muscarinic acetylcholine M3 receptor that activates neuronal firing. Perlapine displays >10,000-fold selectivity for hM3Dq over hM3.
| Cas No. | 1977-11-3 | SDF | |
| 别名 | MP-11 | ||
| Canonical SMILES | CN(CC1)CCN1C2=NC(C=CC=C3)=C3CC4=C2C=CC=C4 | ||
| 分子式 | C19H21N3 | 分子量 | 291.4 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 10 mg/ml,DMSO:PBS (pH 7.2) (1:1): 0.5 mg/ml,Ethanol: 5 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4317 mL | 17.1585 mL | 34.3171 mL |
| 5 mM | 0.6863 mL | 3.4317 mL | 6.8634 mL |
| 10 mM | 0.3432 mL | 1.7159 mL | 3.4317 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Perlapine and dopamine metabolism: prediction of antipsychotic efficacy
Eur J Pharmacol 1977 Jan 7;41(1):65-72.PMID:12986DOI:10.1016/0014-2999(77)90372-7.
A model for the prediction of antipsychotic efficacy based on the dose-dependent increase in levels of 3,4-dihydroxyphenylacetic acid (DOPAC) in the striatum and tuberculum olfactorium of the rat is presented. The effect of Perlapine, a sleep-promoting and sedative agent reported to lack antipsychotic efficacy, was compared in this system to haloperidol, chlorpromazine and clozapine. All four drugs produced a dose-dependent increase in DOPAC in the two dopamine-rich structures. The potency of Perlapine was similar to that of chlorpromazine. Dopamine, assayed in the striatum and tuberculum olfactorium by a new gas chromatographic procedure was not altered by Perlapine. The time--action curves for Perlapine and clozapine were virtually identical both in the striatum and in the tuberculum olfactorium. All four drugs also elevated homovanillic acid to a similar extent. These results indicate that Perlapine should be re-evaluated clinically. We predict that such trials will reveal that Perlapine does possess antipsychotic efficacy.
Perlapine: relationship between stimulation of prolactin secretion and antipsychotic activity
Psychopharmacology (Berl) 1977 Oct 20;54(2):183-6.PMID:412213DOI:10.1007/BF00426777.
Perlapine is a dibenzohetereopine compound chemically related to clothiapine, loxapine, and clozapine. Although the latter three compounds are antipsychotic, Perlapine has not been reported to be antipsychotic. Nevertheless, all four drugs increase rat plasma prolactin levels. The order of potency is loxapine, Perlapine, clothiapine, and clozapine. These results suggest that either Perlapine should be reexamined for antipsychotic properties or there are hitherto unsuspected discrepancies between the dopamine receptors relevant to antipsychotic activity in man and those that regulate prolactin secretion in the rat.
Effects of clozapine, thioridazine, Perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat
Psychopharmacologia 1975;41(1):27-33.PMID:235767DOI:10.1007/BF00421302.
The effects of clozapine, thioridazine, Perlapine and haloperidol on the metabolism of the biogenic amines in the brain of the rat have been investigated. Haloperidol, Perlapine and thioridazine induce catalepsy and enhance the turnover of DA in the striatum as indicated by the dose-dependent increase in the DA-metabolites, HVA and DOPAC. These effects are due to blockade of dopaminergic transmission, haloperidol being far more potent than Perlapine or thiridazine. Clozapine differs from these agents in that it elevates the concentration of striatal DA. The increase of the concentrations of HVA and DOPAC by clozapine is not accompanied by development of catalepsy. Therefore, clozapine seems to influence striatal DA by a mechanism other than DA-receptor blockade. All four drugs enhance the turnover of NA in the brain stem. This effect is probably secondary to the blockade of NA-receptors. There was no correlation between the effects on NA-metabolism and the EEG-arousal inhibitory activities of these agents or their clinical antipsychotic effects. Clozapine increase the concentration of 5-HT and 5-HIAA in the brain. This effect was not seen with the other drugs. Perlapine seems to enhance the turnover of 5-HT, whereas haloperidol reduced the 5-HT concentration. Thioridazine appears to have no effect on the metabolism of 5-HT.
Atypical neuroleptics have low affinity for dopamine D2 receptors or are selective for D4 receptors
Neuropsychopharmacology 1997 Feb;16(2):93-110; discussion 111-35.PMID:9015795DOI:10.1016/S0893-133X(96)00187-X.
This review examines the possible receptor basis of the atypical action of those atypical antipsychotic drugs that elicit low levels of Parkinsonism. Such an examination requires consistent and accurate dissociation constants for the antipsychotic drugs at the relevant dopamine and serotonin receptors. It has long been known, however, that the dissociation constant of a given antipsychotic drug at the dopamine D2 receptor varies between laboratories. Although such variation depends on several factors, it has recently been recognized that the radioligand used to measure the competition between the antipsychotic drug and the radioligand is an important variable. The present review summarizes information on this radioligand dependence. In general, a radioligand of low solubility in the membrane (i.e., low tissue:buffer partition) results in a low value for the antipsychotic dissociation constant when the drug competes with the radioligand. Hence, by first obtaining the antipsychotic dissociation constants using different radioligands of different solubility in the membrane, one can then extrapolate the data to low or "zero" ligand solubility. The extrapolated value represents the radioligand-independent dissociation constant of the antipsychotic. These values are here given for dopamine D2 and D4 receptors, as well as for serotonin 5-HT2A receptors. These values, moreover, agree with the dissociation constant directly obtained with the radioactive antipsychotic itself. For example, clozapine revealed a radioligand-independent value of 1.6 nM at the dopamine D4 receptor, agreeing with the value directly measured with [3H]-clozapine at D4. However, because clozapine competes with endogenous dopamine, the in vivo concentration of clozapine (to occupy dopamine D4 receptors) can be derived to be about 13 nM, agreeing with the value of 12 to 20 nM in the plasma water or spinal fluid observed in treated patients. The atypical neuroleptics remoxipride, clozapine, Perlapine, seroquel, and melperone had low affinity for the dopamine D2 receptor (radioligand-independent dissociation constants of 30 to 90 nM). Such low affinity makes these latter five drugs readily displaceable by high levels of endogenous dopamine in the caudate or putamen. Most typical neuroleptics have radioligand-independent values of 0.3 to 5 nM at dopamine D2 receptors, making them more resistant to displacement by endogenous dopamine. Finally, a relation was found between the neuroleptic doses for rat catalepsy and the D2:D4 ratio of the radioligand-independent K values for these two receptors. Thus, the atypical neuroleptics appear to fall into two groups, those that have a low affinity for dopamine D2 receptors and those that are selective for dopamine D4 receptors.
Chemogenetic activation of VGLUT3-expressing neurons decreases movement
Eur J Pharmacol 2022 Nov 15;935:175298.PMID:36198338DOI:10.1016/j.ejphar.2022.175298.
Vesicular glutamate transporters (VGLUTs) are responsible for the storage of glutamate into secretory vesicles. The VGLUT3 isoform is mainly expressed in neurons that secrete other classical neurotransmitters, including the cholinergic interneurons in the striatum, and VGLUT3-expressing neurons often secrete two distinct neurotransmitters. VGLUT3 is discretely distributed throughout the brain and is found in subpopulations of spinal cord interneurons, in subset of neurons in the dorsal root ganglion, and in Merkel cells. Mice with a global loss of VGLUT3 are hyperactive and the modulation of specific VGLUT3-expressing circuits can lead to changes in movement. In this study, we tested the hypothesis that increased activity of VGLUT3-expressing neurons is associated with decreased movement. Using a mouse line expressing excitatory designer receptor exclusively activated by designer drugs (hM3Dq-DREADD) on VGLUT3-expressing neurons, we showed that activation of hM3Dq signalling acutely decreased locomotor activity. This decreased locomotion was likely not due to circuit changes mediated by glutamate nor acetylcholine released from VGLUT3-expressing neurons, as activation of hM3Dq signalling in mice that do not release glutamate or acetylcholine from VGLUT3-expressing neurons also decreased locomotor activity. This suggests that other neurotransmitters are likely driving this hypoactive phenotype. We used these mouse lines to compare the effects of DREADD agonists in vivo. We observed that clozapine-N-oxide (CNO), clozapine, compound 21 and Perlapine show small differences in the speed at which they prompt behavioural responses but the four of them are selective DREADD ligands.