Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MONOAMINE OXIDASE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed2005

Differential functional variability of serotonin transporter and monoamine oxidase a genes in macaque species displaying contrasting levels of aggression-related behavior.

Functional allelic variation in the transcriptional control region of the serotonin transporter and monoamine oxidase A genes has been associated with anxiety- and aggression-related behavior in humans and, more recently, in nonhuman primates. Here, we have genotyped these polymorphic regions in seven species of the genus Macaca. Macaques exhibit exceptional inter-species variation in aggression-related social behavior as illustrated by recent studies showing overlapping patterns of aggression-based social organization grades and macaque phylogeny. We cloned and sequenced two new alleles of the serotonin transporter gene-linked polymorphic region in Barbary and Tibetan macaques. In addition, we observed that species displaying tolerant societies, with relaxed dominance and high levels of conciliatory tendency, were monomorphic for both the serotonin transporter gene and, with the exception of Tonkean macaques, the monoamine oxidase A gene. In contrast, those species known to exhibit intolerant, hierarchical and nepotistic societies were polymorphic at one or more of these loci. Rhesus (M. mulatta), the most intolerant and hierarchical species of macaques, showed the greatest degree of allelic variation in both genes. Additional investigation of a polymorphic repeat in exon III of the dopamine receptor D4 as well as a repeat/single nucleotide polymorphism in the 3' untranslated region of the dopamine transporter which have both been implicated in the modulation of complex behavior failed to reveal a relationship between allelic variability and social organization grade. Taken together, these findings suggest that genetic variation of serotonergic neurotransmission may play an important role in determining inter-species differences in aggression related behavior in macaques.

Aggression↗
PubMed1982

Some properties of monoamine oxidase and a semicarbazide sensitive amine oxidase capable of the deamination of 5-hydroxytryptamine from porcine dental pulp.

The deamination of 5-hydroxytryptamine, tryptamine and benzylamine by porcine dental pulp membrane preparations is brought about not only by monoamine oxidase, but also by a clorgyline (and deprenyl) resistant), semicarbazide sensitive enzyme. The semicarbazide sensitive enzyme was also inhibited by aminoguanidine, hydroxylamine and phenylhydrazine, but was not affected to any significant extent by incubation at 50 degrees for up to 100 min. There was, on the other hand, considerable inhibition of monoamine oxidase activity after incubation at this temperature. The semicarbazide sensitive enzyme neither metabolised, nor was inhibited by putrescine or cadaverine. Mixed substrate experiments indicated that 5-hydroxytryptamine and tryptamine interacted at the same catalytic centre on the semicarbazide sensitive enzyme.

Amine Oxidase (Copper-Containing)↗
PubMed1987

Psychiatric morbidity and platelet monoamine oxidase activity in cancer patients.

Psychometric ratings for both anxiety and depression in 30 cancer patients were significantly elevated compared with values in 16 controls. The scores were especially high in the 14 patients who did not have breast cancer. This group also had significantly greater platelet monoamine oxidase activity than either the breast cancer patients or controls. Platelet monoamine oxidase activity values correlated significantly with both depression and anxiety scores in the whole cancer group.

Adult↗
PubMed2005

Fluorinated phenylcyclopropylamines. Part 4: effects of aryl substituents and stereochemistry on the inhibition of monoamine oxidases by 1-aryl-2-fluoro-cyclopropylamines.

A series of para-ring-substituted (E)- and (Z)-1-aryl-2-fluorocyclopropylamines were examined as inhibitors of recombinant human liver monoamine oxidase A (MAO A) and B (MAO B). Unlike the parent 1-phenylcyclopropylamine, which is a selective inhibitor of MAO B, both (E)- and (Z)-diastereomers of derivatives having fluorine at the 2-position of the cyclopropane ring were potent and selective irreversible inhibitors of MAO A. Both electron releasing groups (Me, OMe) and electron attracting groups (Cl, F) substituted in the para-position caused a modest increase in activity. Geminal difluoro-substitution caused a loss of potency of 100-fold compared to either (E)- or (Z)-monofluorinated analogue. Surprisingly, (1S,2R)-2-fluoro-1-phenylcyclopropylamine and the (1R,2S)-enantiomer were essential equally potent as inhibitors of MAO A and MAO B. None of the tested 1-aryl-2-fluorocyclopropylamines exhibited significant inhibition of tyramine oxidase.

Crystallography, X-Ray↗
PubMed1987

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain. Thus, as demonstrated here, NPB was found to be as potent as pargyline and deprenyl with regard to its in vivo MAO type B inhibitory properties.

Animals↗
PubMed2001

Excessive activation of serotonin (5-HT) 1B receptors disrupts the formation of sensory maps in monoamine oxidase a and 5-ht transporter knock-out mice.

Deficiency in the monoamine degradation enzyme monoamine oxidase A (MAOA) or prenatal exposure to the monoamine uptake inhibitor cocaine alters behavior in humans and rodents, but the mechanisms are unclear. In MAOA knock-out mice, inhibiting serotonin synthesis during development can prevent abnormal segregation of axons in the retinogeniculate and somatosensory thalamocortical systems. To investigate this effect, we crossed MAOA knock-outs with mice lacking the serotonin transporter 5-HTT or the 5-HT1B receptor, two molecules present in developing sensory projections. Segregation was abnormal in 5-HTT knock-outs and MAOA/5-HTT double knock-outs but was normalized in MAOA/5-HT1B double knock-outs and MAOA/5-HTT/5-HT1B triple knock-outs. This demonstrates that the 5-HT1B receptor is a key factor in abnormal segregation of sensory projections and suggests that serotonergic drugs represent a risk for the development of these projections. We also found that the 5-HT1B receptor has an adverse developmental impact on beam-walking behavior in MAOA knock-outs. Finally, because the 5-HT1B receptor inhibits glutamate release, our results suggest that visual and somatosensory projections must release glutamate for proper segregation.

Animals↗
PubMed1986

Suppression of the hypo- and hyperthermic responses to 5-HT agonists following the repeated administration of monoamine oxidase inhibitors.

Hypo- and hyperthermic responses resulting from the activation of putative 5-HT1A and 5-HT2 receptors, respectively, were examined after the chronic treatment of rats with monoamine oxidase inhibitors. The treatment of rats for 4 or 7 days with nialamide (40 mg/kg, twice daily) resulted in a suppression of the hypothermic effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.05-0.25 mg/kg, SC). The decrease in body temperature elicited by a low dose of 5-methoxy-N, N-dimethyltryptamine (5MeODMT, 1 mg/kg) also was diminished in rats treated chronically with nialamide. The administration of a high dose of 5MeODMT (5 mg/kg) resulted in a hyperthermic response, which was also attenuated after the repeated administration of nialamide. The repeated administration of clorgyline (a selective inhibitor of type A MAO) or deprenyl (a selective inhibitor of type B MAO) failed to alter the hypothermic effect of 8-OH-DPAT. However, in animals treated chronically with both clorgyline and deprenyl, a suppressed response to 8-OH-DPAT was observed. In view of the concept that the hypo- and hyperthermic responses to 5-HT agonists are mediated by 5-HT1A and 5-HT2 receptor subtypes, respectively, it is concluded that the responsiveness of these 5-HT receptor subtypes involved in thermoregulatory responses is decreased following chronic treatment of rats with monoamine oxidase inhibitors. It appears that inhibition of both type A and B MAO is necessary for this desensitization process.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Effects of long-term treatment with dicyclic, tricyclic, tetracyclic, and noncyclic antidepressant drugs on monoamine oxidase activity in mouse brain.

1. The individual long-term effects of the antidepressant drugs zimeldine, viloxazine, imipramine, amitriptyline, nortriptyline, maprotiline, or nomifensine, on brain mitochondrial monoamine oxidase (MAO) activity, were studied in mice that were given daily intraperitoneal injections (30 mg/kg) of these reagents for 4 weeks. 2. Both the A-form (MAO-A) and B-form (MAO-B) of MAO were inhibited after long-term administration of all the drugs except nortriptyline (MAO-A was not affected) and maprotiline (neither MAO-A nor MAO-B were affected). 3. Kinetic analysis showed a significant decrease in Vmax values, and an increase in K(m) values for MAO-B during treatment. 4. All seven drugs are competitive inhibitors of MAO-A, noncompetitive inhibitors of MAO-B, and were more potent in vitro for MAO-B. 5. MAO-A was inhibited by the following drugs (in ascending order of potency) : nortriptyline, amitriptyline, imipramine, maprotiline, zimeldine, nomifensine, and viloxazine. 6. MAO-B was inhibited by the following drugs (in ascending order of potency): nortriptyline, imipramine, maprotiline, amitriptyline, zimeldine, nomifensine, and viloxazine.

Animals↗
PubMed1984

Histochemical investigation of criteria for the distinction between monoamine oxidase A and B in various species.

The superior cervical ganglion (SCG), pineal body (PB), and liver (L) of the rat, rabbit and cat were stained for monoamine oxidase (MAO) A and B by the tetranitro blue tetrazolium (TNBT) and coupled peroxidase ( PerOx ) methods, using 5-hydroxytryptamine (5HT), tryptamine ( Tryp ), tyramine (Tyr), and benzylamine (Bz) as substrates, and clorgyline (Cl) and deprenyl (Dep), both at 10(-7) M, as selective inhibitors. The nodose ganglion (NG) and dorsal root ganglion (DRG) of the rabbit and cat were also studied. The results with rat tissues were consistent with published quantitative findings (SCG, MAO-A much greater than B; PB, MAO-A less than or equal to B; L, MAO-A = B). In the rabbit, the findings with the SCG were similar; the MAO activities of the PB were relatively resistant to both inhibitors; the MAO of the liver required 10(-4) M concentrations of both inhibitors to produce near total inhibition, suggesting that the liver contains an MAO distinct from MAO A and B. All cat tissues examined appeared to contain almost exclusively MAO-B. In this species 5HT, which is generally considered a selective substrate for MAO-A, was oxidized by MAO-B. The findings indicate that criteria for MAO-A, -B, and other subgroups must be defined for each species and tissue.

Animals↗
PubMed2002

Synthesis and characterization of radioiodinated MD-230254: a new ligand for potential imaging of monoamine oxidase B activity by single photon emission computed tomography.

A series of iodinated analogues of MD-230254 was synthesized and evaluated for inhibitory potency and selectivity toward monoamine oxidase B (MAO-B). Among them, 5-[4-(2-iodobenzyloxy)phenyl]-3-(cyanoethyl)-1,3,4-oxadiazole-2(3H)one (2-IBPO) was found to have high inhibitory potency and selectivity toward MAO-B (IC50=2.0 nM, MAO-A/MAO-B >50000). Analysis of the inhibition kinetics indicated that 2-IBPO acts in a two-step mechanism as a competitive, slow, and tight-binding inhibitor of MAO-B with a Ki value of 2.4 nM and an overall Ki* value at an equilibrium of 3.8 nM. The new radioligand for MAO-B, [125I]2-IBPO was conveniently synthesized from a tributylstannyl precursor by an iododestannylation reaction using sodium [125I]iodide and hydrogen peroxide with high radiochemical yield. The in vivo tissue distribution studies of [125I]2-IBPO demonstrated its high initial uptake and prolonged retention in the brain. A selective interaction of [125I]2-IBPO with MAO-B was confirmed by the pretreatment experiment with well known MAO specific inhibitors, l-deprenyl, Ro-16-6491, clorgyline, and Ro-41-1049. These very desirable characteristics of [125I]2-IBPO suggested that a 123I-labeled counterpart, [123I]2-IBPO, would have great potential in in vivo studies of MAO-B in the human brain with single photon emission computed tomography (SPECT).

Animals↗
PubMed1985

Mechanism for reactivation of N-cyclopropylbenzylamine-inactivated monoamine oxidase by amines.

The effect of 18 different amines, two mercaptans, and two alcohols on the reactivation of N-cyclopropylbenzylamine- (N-CBA-) inactivated bovine liver monoamine oxidase (MAO) is described. All of the compounds that reactivate the enzyme produce a time-dependent pseudo-first-order return of enzyme activity and exhibit saturation kinetics. There is no direct correlation between the ability of a compound to serve as a substrate for native MAO and its ability to reactivate N-CBA-inactivated MAO. Amines containing an aromatic moiety, in general, are better reactivators than the aliphatic amines. The amine must be primary or secondary in order for reactivation to occur. The distance between the aromatic portion and the amino group is critical to the reactivation properties of the compound. The mercaptans and alcohols do not reactivate N-CBA-inactivated MAO, nor do they interfere with the reactivation reaction by benzylamine. Three mechanisms for the reactivation reaction are considered. One involves initial Schiff base formation with the active site adduct produced by N-CBA inactivation of MAO followed by base-catalyzed beta-elimination to the imine of acrolein. The second mechanism is the same as the first except no prior Schiff base formation is invoked. The third mechanism is an SN2 displacement by the amine of the active site amino acid residue attached to the adduct. Experiments are carried out to exclude the SN2 mechanism. The results of the reactivation experiments favor the Shiff base mechanism.

Amines↗
PubMed1980

The presence of the type A form of monoamine oxidase within nigrostriatal dopamine-containing neurons.

The nigrostriatal dopaminergic pathway was selected as a model system to determine the form (i.e., type A or B) of monoamine oxidase (MAO) present within central dopamine (DA)-containing neurons. The preferential accumulation and subsequent intraneuronal deamination of [14C]DA by striatal synaptosomes was examined in synaptosomal-rich homogenates obtained from rats previously treated (i.v.) with graded doses of either clorgyline or deprenyl. To confirm the selective MAO inhibitor properties of clorgyline or deprenyl, type A and B MAO activity was simultaneously assayed in striatal aliquots of the same tissue pool. The selective inhibition of type A MAO by clorgyline was associated wih a decline in the synaptosomal deamination of [14C]DA. These results were further substantiated by experiments performed on the synaptosomal deamination of [3H]DA, newly synthetized from [3H]tyrosine in the presence of either clorgyline or deprenyl. The deamination of newly synthetized [3H]DA was reduced by the selective inhibition of type A MAO. Finally, the destruction of DA-containing nigrostriatal neurons by the stereotaxic administration of 6-hydroxydopamine produced a selective reduction in the type A MAO activity in the striatum ipsilateral to the 6-hydroxydopamine-injected substantia nigra. A high correlation was obtained between the size of the DA-containing neuronal lesion and the reduction in type A MAO activity. No reduction in type B MAO activity was observed. These results strongly indicate the presence of the type A form of MAO within nigrostriatal dopaminergic neurons of the rat brain.

Animals↗
PubMed1990

Effects of N- and C-terminal fragments of substance P on ATPase and monoamine oxidase activities in rat brain.

The in vitro influence of substance P (SP) C- and N-terminal fragments on the Na+,K(+)-ATPase and Ca2+,Mg2(+)-ATPase and monoamine oxidase (MAO) from synaptosomal membrane and extra-synaptosomal mitochondria were studied. The obtained results indicate: 1. C-terminal fragment of SP (SP6-11) in 10 microM concentration stimulates the Ca2+,Mg2(+)-ATPase activities from cerebral cortex and hippocampus. Na+,K(+)-ATPase from cerebral cortex is hardly sensitive to the action of this fragment. 2. N-terminal fragment of SP (SP1-5) in 10 microM concentration increases Na+,K(+)-ATPase activity from cerebral cortex and hippocampus. 3. N-terminal tetrapeptide (SP1-4) exerts no influence on ATPases independently from their brain localization. 4. The activity of monoamine oxidase after use of C- and N-terminal fragments is unchanged.

Adenosine Triphosphatases↗
PubMed1988

[3H]Ro 16-6491, a selective probe for affinity labelling of monoamine oxidase type B in human brain and platelet membranes.

[3H]Ro 16-6491 [N-(2-aminoethyl)-p-chlorobenzamide HCl], a reversible "mechanism-based" inhibitor of monoamine oxidase (MAO) type B, binds selectively and with high affinity to the active site of MAO-B in brain and platelet membranes. Under normal conditions, the binding of [3H]Ro 16-6491 is fully reversible. However, [3H]Ro 16-6491 could be irreversibly bound (covalently) to membranes by the addition of the reducing agent NaBH3CN to the sample and adjusting to pH 4.5 with acetic acid. No irreversible labelling occurred in the absence of NaBH3CN and at neutral pH. The presence of the irreversible MAO-B inhibitor l-deprenyl completely abolished the irreversible labelling of the membranes by [3H]Ro 16-6491. The selective inactivation of MAO-B, e.g., by l-deprenyl prevented the covalent incorporation of [3H]Ro 16-6491 whereas selective inhibition of the MAO-A by clorgyline was without effect. The covalent linkage to membranes of unlabelled Ro 16-6491 and Ro 19-6327 (a selective and reversible MAO-B inhibitor closely related to Ro 16-6491) after the addition of NaBH3CN at pH 4.5 irreversibly inactivated MAO-B activity whereas MAO-A activity was unaffected. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis of labelled membranes showed that [3H]Ro 16-6491 was incorporated into a single polypeptide with a molecular mass identical to the one labelled by [3H]pargyline (58 kilodaltons). Our results indicate that the polypeptide that is covalently labelled by [3H]Ro 16-6491 corresponds to one of the two MAO-B subunits.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1999

Inhibition of monoamine oxidase type A, but not type B, is an effective means of inducing anticonvulsant activity in the kindling model of epilepsy.

The anticonvulsant activity of inhibitors of monoamine oxidase (MAO) was reported early after the development of irreversible MAO inhibitors such as tranylcypromine, but was never clinically used because of the adverse effects of these compounds. The more recently developed reversible MAO inhibitors with selectivity for either the MAO-A or MAO-B isoenzyme forms have not been studied extensively in animal models of epilepsy, so it is not known which type of MAO inhibitor is particularly effective in this respect. We compared the following drugs in the kindling model of epilepsy: 1) L-deprenyl (selegiline), i.e., an irreversible inhibitor of MAO-B, which, however, also inhibits MAO-A at higher doses, 2) the novel reversible MAO-B inhibitor LU 53439 (3,4-dimethyl-7-(2-isopropyl-1,3, 4-thiadiazol-5-yl)-methoxy-coumarin), which is much more selective for MAO-B than L-deprenyl, 3) the novel reversible and highly selective MAO-A inhibitor LU 43839 (esuprone; 7-hydroxy-3, 4-dimethylcoumarin ethanesulfonate), and 4) the irreversible nonselective MAO inhibitor tranylcypromine. Esuprone proved to be an effective anticonvulsant in the kindling model with a similar potency as L-deprenyl. In contrast to esuprone and L-deprenyl, the selective MAO-B inhibitor LU 53439 was not effective in the kindling model; this substantiates the previous notion that the anticonvulsant activity of L-deprenyl is not related to MAO-B inhibition, but to other effects of this drug, such as inhibition of MAO-A. Drugs inhibiting both MAO-A and MAO-B to a similar extent (tranylcypromine) or combinations of selective MAO-A and MAO-B inhibitors (esuprone plus LU 53439) had no advantage over MAO-A inhibition alone, but were less well tolerated. The data thus suggest that selective MAO-A inhibitors such as esuprone may be an interesting new approach for the treatment of epilepsy.

Animals↗
PubMed1989

Inhibition of monoamine oxidase by analogues of amiloride.

Amiloride analogues with nonaromatic substituents on the 5-amino group or different substituents on carbon-6 of the pyrazine ring were tested as inhibitors of monoamine oxidase A and B in rat brain homogenate. The inhibition was competitive and reversible. 5-(N,N-Tetramethylene)amiloride protected the A type in the homogenate against irreversible inhibition by clorgyline. A reciprocal relation was found to exist between inhibitory constants of 5-N-substituted amiloride analogues for monoamine oxidase A and the ratio of overflows of endogenous noradrenaline and 3,4-dihydroxyphenylethylene glycol from the isolated rat tail artery incubated in the presence of a 50 microM concentration of the analogue, when the tissue was exposed to 10 microM tyramine. The 5-amino group appeared to be essential for inhibition of the A but not of the B type. Bell-shaped relations between inhibitory constants of 5-(N-alkyl)- and 5-(N,N-dialkyl)-substituted analogues and lengths of alkyl chains were different for each type. The presence of a methyl group in the alpha-position of the chain increased substantially the inhibitory constant for the A type. Halogen atoms as substituents on carbon-6 increased inhibitory constants for both types of the enzyme in the sequence: I less than Br less than Cl less than F. These findings are consistent with the existence of hydrophobic binding sites of restricted dimensions in both types of the enzyme.

Adrenergic Fibers↗
PubMed1984

Effects of tricyclic antidepressants on platelet monoamine oxidase activity.

The eight subjects in this study were diagnosed as having primary or secondary depression and were treated with amitriptyline, 100 to 300 mg/day. Activity of platelet monoamine oxidase (MAO), an enzyme responsible for the degradation of biogenic amines, was determined before and after treatment with amitriptyline. Pretreatment values for MAO activity ranged from 17.94 to 44.89 U. After amitriptyline the values ranged from 0.66 to 41.94 U, a mean decrease of 50.2%. These results are consistent with the hypothesis that the tricyclic antidepressants act, at least in part, by inhibition of MAO.

Adolescent↗
PubMed1998

Mechanism-based inhibition of monoamine oxidase by 3-aryl-Delta3-pyrrolines.

The compound 1-methyl-3-phenyl-Delta3-pyrroline and its 4-chlorophenyl analogue appear to act as irreversible inhibitors of monoamine oxidase B (MAO B) in mitochondria of rat liver. The compounds are metabolized by MAO B and concomitantly inhibit the enzyme in what seems to be a two-step process. The metabolic end product of this process is the corresponding pyrrole. This inhibition process is considered in the light of possible intermediates formed during the enzymic oxidation, and comparisons are made with the structurally analogous neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

Animals↗