(+)-4-dimethylamino-2, α-dimethylphenethylamine (FLA 336(+)), a selective inhibitor of the a form of monoamine oxidase in the rat brain

Ask, Anna‐Lena; Hogberg, Kerstin; Schmidt, Lennart; Klessling, Hans; Ross, Svante B.

doi:10.1016/0006-2952(82)90035-1

Cited by 54 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The development ofspecific inhibitors ofthe transport mechanisms responsible for the re-uptake of released transmitter amines in the monoaminergic nerve terminals, has made it possible to measure the deamination of radiolabelled biogenic amines inside specific aminergic synaptosomes when a low concentration of the substrate is added to a synaptosomal preparation (Ross & Ask, 1980;Ask et al, 1982c;. Thus, the difference between the deamination of the added substrate in the absence and presence of the uptake inhibitor is a measure ofthe deamination ofthe substrate after being transported into these synap- ' Correspondence. tosomes.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of monoamine oxidase in 5‐ hydroxytryptaminergic neurones by substituted p‐aminophenylalkylamines

Ask

Fagervall

Florvall

et al. 1985

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 A series of substituted p-aminophenethylamines and some related compounds were examined with regards to the inhibition ofmonoamine oxidase (MAO) in vivo inside and outside 5-hydroxytryptaminergic neurones in the rat hypothalamus. This was recorded as the protection against the irreversible inhibition of MAO produced by phenelzine by determining the remaining deaminating activity in the absence and presence of citalopram using a low (0.1 yIM) concentration of ['4CJ-5-hydroxytryptamine (5-HT) as substrate. 2 Some of the phenethylamines were much more potent inside than outside the 5-hydroxytryptaminergic neurones. This neuronal selectivity was antagonized by pretreatment of the rats with norzimeldine, a 5-HT uptake inhibitor, which indicates that these compounds are accumulated in the 5-HT nerve terminals by the 5-HT pump. 3 Selectivity was obtained for compounds with dimethyl, monomethyl or unsubstituted p-amino groups. An isopropyl group appears to substitute for the dimethylamino group but with considerably lower potency. Compounds with 2-substitution showed selectivity for aminergic neurones and this effect decreased with increased size of the substituent. The 2,6-dichloro derivative FLA 365 had, however, no neuronal selective action but was a potent MAO inhibitor. Substitutions in the 3-and 5-positions decreased both potency and selectivity. 4 Prolongation of the side chain with one methylene group abolished the preference for the MAO in 5-hydroxytryptaminergic neurones although the MAO inhibitory potency remained. The selectivity disappeared by increasing the a-substituent to an ethyl group but remained for the oco-dimethyl substituted derivatives. 5 It is concluded that compounds which are (1) transported by the 5-HT pump and (2) potent reversible MAO-A inhibitors produce pronounced inhibition of MAO in 5-hydroxytryptaminergic neurones.

show abstract

Section: Introductionmentioning

confidence: 99%

Inhibition of monoamine oxidase in 5‐ hydroxytryptaminergic neurones by substituted p‐aminophenylalkylamines

Ask

Fagervall

Florvall

et al. 1985

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Amiflamine has been shown to be a specific MAO-A inhibitor exhibiting both competitive and reversible properties in rats (3,4) and in humans (6, 8).…”

Section: Discussionmentioning

confidence: 99%

“…Amiflamine is a reversible inhibitor of MAO A which is reported to exhibit additional selectivity by accumulating in the serotonergic neurons in the brain (3)(4)(5)(6). In the present investigation, the effect of amiflamine on tyramine metabolism by the dog gut has been studied.…”

Section: Accepted May 8 1986mentioning

confidence: 99%

The Effects of Amiflamine, a Reversible MAO-A Inhibitor, on the First Pass Metabolism of Tyramine in Dog Intestine

Yasuhara

Kiuchi

Oguchi

et al. 1986

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

Abstract-The effects of amiflamine on tyramine deamination were studied using isolated loops of intestine in anesthetized dogs.In the pretreatment experiment, dogs were dosed with amiflamine (3.5 mg/kg/day) once daily for 3 days, with the study being carried out 3 hr after the final dose.[14C] Tyramine (50 mg and 50 /cCi) in 10 ml of normal saline was introduced into the isolated loops of gut, and tyramine and p-hydroxyphenylacetic acid in the venous blood were separated by HPLC and measured by scintillation spectrometry.In the untreated dogs, ap proximately 15% of the tyramine passed through the gut wall unchanged. When tyramine and amiflamine (0.06 to 3.5 mg/kg) were administered simultaneously to the gut loop, about 27 to 65% of the tyramine passed through the gut wall un changed.On the contrary, after pretreatment with amiflamine for 3 days, percen tage of tyramine passing through the gut wall was not increased in comparison with the control.These results suggest that pretreatment with amiflamine does not produce drug concentrations in the lining cells of the gut sufficient to effectively inhibit the deamination of oral tyramine, which is administered at least 3 hr after the final dose of amiflamine.Monoamine oxidase (MAO) inhibitors are clinically used as antidepressants, but limitation of extensive use of these drugs is due to hypertensive crisis (cheese effect) occurring when the patient ingests certain foodstuff containing vasoactive amines such as tyramine. Circulating tyramine liberates noradrenaline from nerve endings and produces the pressor effect (1 ). It is generally assumed that such hypertensive crises occur as a result of inhibition of MAO in the intestine and to a lesser extent in the liver, allowing active tyramine to enter the systemic circulation, and of inhibition of intraneural

show abstract

“…Since mitochondrial MAO is believed to exist in many tissues in two functional forms called A and B-form MAO (28,29), many investigators have studied the inhibition of A-form and B-form MAO by various reagents (30)(31)(32).…”

Section: Effects Of Mp Ap Oh-mp and Oh-ap On Mao Activity In Vitromentioning

confidence: 99%

Effects of d-methamphetamine on monkey brain monoamine oxidase, in vivo and in vitro.

1987

View full text Add to dashboard Cite

Abstract-A and B form MAO activities in mitochondria and synaptosome were measured in the brain of monkeys administered d-methamphetamine (d-MP) 2 mg/kg, i.m., daily for 7 days. When mitochondria were used as an enzyme pre paration, the Km and Vmax values decreased with 5-HT (serotonin for A-form MAO substrate) and i3-phenylethylamine ((3-PEA for B-form MAO substrate), while in the synaptosome, a significant increase of the Km and Vmax values was observed with 5-HT and dopamine as substrates. The mitochondrial MAO treated with d-MP was inhibited strongly by clorgyline and deprenyl with ,3-PEA as a substrate , while synaptosomal MAO was highly sensitive to these MAO inhibitors with 5-HT as a substrate. MP and amphetamine (AP) were found in brain mitochondrial and synaptosomal preparations of monkeys administered 2 mg/kg d-MP, i.m. daily for 7 days; MP and AP contents were 5.05±0.22 pg/mg protein and 37.3±3.8 ng/mg protein in mitochondria and 2.35±0.35 pg/mg protein and 46.4±1.5 ng/mg protein in synaptosomes, respectively. MAO was inhibited by MP and its metabolites, AP, p-hydroxymethamphetamine (OH-MP) and p-hydroxyamphetamine (OH-AP), with 5-HT, ,3-PEA and dopamine as substrates , in vitro. MP and its metabolites were more potent inhibitors of A-form MAO than B-form MAO.

show abstract

(+)-4-dimethylamino-2, α-dimethylphenethylamine (FLA 336(+)), a selective inhibitor of the a form of monoamine oxidase in the rat brain

Cited by 54 publications

References 9 publications

Inhibition of monoamine oxidase in 5‐ hydroxytryptaminergic neurones by substituted p‐aminophenylalkylamines

Inhibition of monoamine oxidase in 5‐ hydroxytryptaminergic neurones by substituted p‐aminophenylalkylamines

The Effects of Amiflamine, a Reversible MAO-A Inhibitor, on the First Pass Metabolism of Tyramine in Dog Intestine

Effects of d-methamphetamine on monkey brain monoamine oxidase, in vivo and in vitro.

Contact Info

Product

Resources

About