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| Other names | PBMA; 4-Bromomethamphetamine; 4-BMA;p-Bromomethamphetamine;p-BMA; V-111; 4-Bromo-N-methylamphetamine; 4-Bromo-N-methylphenylisopropylamine |
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| Formula | C10H14BrN |
| Molar mass | 228.133 g·mol−1 |
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para-Bromomethamphetamine (PBMA; developmental code nameV-111), also known as4-bromomethamphetamine (4-BMA), is amonoaminergicdrug of theamphetamine family related topara-chloroamphetamine (PCA; 4-chloroamphetamine).[1][2][3][4] It was studied byJózsef Knoll and colleagues in the 1970s and 1980s.[1][3][5]
Originally thought toselectively act onserotonin, PBMA was subsequently found to act not only on serotonin but also onnorepinephrine anddopamine similarly to PCA.[4][6][7] It has been reported to producepharmacological effects that have been said to be "somewhat similar" or "indistinguishable" to those oflysergic acid diethylamide (LSD) and various otherhallucinogens in various animal species.[1][7][4][3] However, when the drug was subsequently tested in humans, it showed no hallucinogenic effects whatsoever.[1] This is analogous to the case of PCA, which can produce thehead-twitch response in rodents but is not hallucinogenic in humans.[8][9][10][11][1][12] The hallucinogen-like effects of PBMA in animals can be reversed by the serotoninsynthesisinhibitorpara-chlorophenylalanine (PCPA), suggesting that they are due to elevation of serotonin levels rather than directserotonin receptoragonism.[13]
Otheranimal studies have found PBMA to producestimulant,appetite suppressant,pro-cognitive-like,anticonvulsant, andsleep-disrupting effects.[7][14][15][4][16] Besides its effects, thepharmacokinetics andmetabolism of PBMA have been studied in rodents.[17][5]
PBMA producesserotonergic neurotoxicity of a similar magnitude to PCA andpara-bromoamphetamine (PBA) in rodents.[2][4] Conversely,para-fluoroamphetamine (PFA; 4-fluoroamphetamine) is much less effective.[2][1]
3.5.3. 4-Bromo-N-methylphenylisopropylamine: The bromo-counterparts of the chlorophenylisopropylamine have been studied, but have not found extensive clinical evaluation. The primary amine 4-bromophenylisopropylamine (4-bromoamphetamine) is, like the 4-chloro-analog 4-CA (79), a long-term depleter of serotonin in the brain (Fuller et al. (1975). The 4-fluoro analog, while still effective biochemically, is not of as long a duration of action. The N-methyl homolog of 4-bromo-phenylisopropylamine has demanded interest from a separate point of view, however. This compound, 4-bromo-N-methylphenylisopropylamine (81, V-111, p-bromomethamphetamine), has been found to give pharmacological profiles in a large number of animal species, which are indistinguishable from those shown by LSD and other psychotomimetics (Knoll et al., 1970). Although much of the literature appearing over the period from 1965 to 1975 refers to (81) as a psychotomimetic, it had apparently never been clinically assayed in man. It is now known that the compound "has no psychotomimetic effect whatsoever in humans" (Knoll, 1974, personal communication). The high pharmacological potency of (V-111) in the biochemistry of serotonin and its apparent enhancement of learning and memory in experimental animals have maintained an active interest in it in the research area.
Amphetamine and methamphetamine, which act primarily by increasing carrier-mediated release of dopamine and norepinephrine, do not provoke head twitches (Corne and Pickering 1967; Silva and Calil 1975; Yamamoto and Ueki 1975; Jacobs et al. 1976; Bedard and Pycock 1977; Halberstadt and Geyer 2013). By contrast, the 5-HT releasing drugs fenfluramine and p-chloroamphetamine (PCA) do produce a robust HTR (Singleton and Marsden 1981; Darmani 1998a). Fenfluramine and PCA are thought to act indirectly, by increasing carrier-mediated release of 5-HT, because the response can be blocked by inhibition of the 5-HT transporter (Balsara et al. 1986; Darmani 1998a) or by depletion of 5-HT (Singleton and Marsden 1981; Balsara et al. 1986). [...] Because indirect 5-HT agonists such as fenfluramine, PCA, and 5-HTP are not hallucinogenic (Van Praag et al. 1971; Brauer et al. 1996; Turner et al. 2006), their effects on HTR can potentially be classified as false-positive responses.
Indirect 5-HT2A agonists such as fenfluramine, p-chloroamphetamine (PCA), and 5-hydroxytryptophan (5-HTP) induce head twitches in rodents (Corne et al. 1963; Singleton and Marsden 1981; Darmani 1998) but do not act as hallucinogens in humans (van Praag et al. 1971; Brauer et al. 1996; Turner et al. 2006), However, overdoses of compounds that increase serotonin (5-HT) release can result in 5-HT syndrome, which sometimes includes hallucinations (Birmes et al. 2003; Evans and Sebastian 2007).
Head-twitch response (HTR) in mice was induced by intracerebroventricular injection of tryptamine (TRA) as well as serotonin (5-HT) and p-chloroamphetamine (PCA). Pretreatment with 5,7-dihydroxytryptamine enhanced both the 5-HT-induced and the TRA-induced HTR. The PCA-induced HTR, however, was attenuated by the drug. On the other hand, pretreatment with 6-hydroxydopamine did not alter the 5-HT response but enhanced both the PCA- and the TRA-induced response. These results suggest that 5-HT may directly stimulate the post-synaptic receptors, while the PCA response may be based on the release of endogenous 5-HT.
While some false positives have been identified, such as fenfluramine, p-chloroamphetamine, and 5-hydroxytryptophan, the test predominantly exhibits specificity for 5-HT2A receptor agonists [15].
The role of 5-HT in mediating the behavioral effects of amphetamine is also not entirely clear. Knoll37 suggested that the psychotomimetic effects obtained with high doses of amphetamine are related to 5-HT metabolism. He observed that the psychotomimetic effects of p-bromomethamphetamine are antagonized by pretreatment with p-chlorophenylalanine, a substance which depletes 5-HT by inhibition of its synthesis. This suggests that 5-HT is necessary to obtain the psychotomimetic effects of amphetamine and data from this study indicate that high concentrations of amphetamine release 5-HT from brain tissue containing 5-HT neurons.