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All 12 posts Subject: BPAP, a catecholamine activity enhancer Please login to post Down

Rhodium
(Chief Bee)
09-09-01 15:25
No 211596
User Picture       BPAP, a catecholamine activity enhancer

This could be something interesting, a compound that increases the activity of catecholamines in the brain (like dopamine), but without being a stimulant itself.

Could somebody more pharmacologically inclined than myself elaborate of the implications of such a substance? It seems to be easy to synthesise, too.

Enantioselective synthesis and absolute configuration of (−)-1-(benzofuran-2-yl)-2-propylaminopentane,
((−)-BPAP), a highly potent and selective catecholaminergic activity enhancer
Takahiro Oka, Takuya Yasusa, Takashi Ando, Mayumi Watanabe, Fumio Yoneda, Toshimasa Ishida and Joseph Knoll
Bioorganic & Medicinal Chemistry 9(5), 1213-1219 (2001) (https://www.rhodium.ws/pdf/bpap.pdf)

Abstract
Enantioselective synthesis and absolute configuration of (−)-1-(benzofuran-2-yl)-2-propylaminopentane ((−)-BPAP), which is a highly potent and selective catecholaminergic activity enhancer (CAE) substance, are described. The synthetic approach consists of the coupling reaction of benzofuran with (R)-N-tosyl-2-propylazirizine or (R)-N-methoxy-N-methylnorvaliamide, followed by appropriate modifications of the resulting coupling products. As the results, (−)-BPAP turned out to have the R configuration, which was finally confirmed by X-ray crystallographic analysis.

Quicksilver
(Hive Bee)
09-09-01 17:11
No 211609
      Re: BPAP, a catecholamine acticity enhancer

More fun stuff to read...

(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release.

Eur J Pharmacol 2001 Jun 15;421(3):181-189

Shimazu S, Takahata K, Katsuki H, Tsunekawa H, Tanigawa A, Yoneda F, Knoll J, Akaike A.

Institute of Research and Development, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Osaka 580-8503, Matsubara, Japan.

"Catecholaminergic and serotoninergic activity enhancer" effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP HCl], a compound with selective and potent "catecholaminergic and serotoninergic activity enhancer" effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (-)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3-10 mg/kg). (-)-BPAP HCl (1-3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (-)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R( )-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390), suggesting that the effects of (-)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (-)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (-)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (-)-BPAP HCl significantly improved ptosis. These findings suggested that a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.

Quicksilver
(Hive Bee)
09-09-01 17:13
No 211610
      Re: BPAP, a catecholamine acticity enhancer

A more biological review... (J Knoll's work seems to be a good starting point to look into)

(-)Deprenyl (Selegiline): past, present and future. Neurobiology (Bp) 2000;8(2):179-199

Knoll J.

Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.

(-)Deprenyl (Selegiline), the N-propargyl analogue of (-)methamphetamine, is the only drug in clinical case which, by enhancing the impulse propagation mediated release of noradrenaline and dopamine in the brain (catecholaminergic activity enhancer, CAE, effect), keeps in small doses without side-effects the catecholaminergic brain system on a higher activity level. (-)Deprenyl stimulates the catecholaminergic neurons selectively in the brain because, in contrast to PEA and the amphetamines which induce the continuous release of noradrenaline and dopamine from their intraneuronal stores, (-)deprenyl is devoid of this property. It is due to the CAE effect that a) the maintenance of rats on (-)deprenyl during the postdevelopmental phase of their life slows the age-related decline of sexual and learning performances and prolongs life significantly; b) patients with early, untreated Parkinson's disease maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers, and when on levodopa plus (-)deprenyl, they live significantly longer than patients on levodopa alone; and c) in patients with moderately severe impairment from Alzheimer's disease, treatment with (-)deprenyl slows the progression of the disease. It is reasonable to expect that a prophylactic low dose administration of a safe catecholaminergic activity enhancer substance during the postdevelopmental phase of life will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson's disease and Alzheimer's disease.

foxy2
(Distinctive Doe)
09-10-01 00:47
No 211720
      Re: BPAP, a catecholamine acticity enhancer

Dam it time to order the Deprenyl!!!

Do Your Part To Win The War

RacerX
(Newbee)
09-10-01 04:06
No 211766
      Re: BPAP, a catecholamine acticity enhancer

I have the Selegiline (Beprynl) does this mean I should be mixing it with say a gram of yabba a day?

Rhodium
(Chief Bee)
09-10-01 11:05
No 211842
User Picture       Re: BPAP, a catecholamine acticity enhancer

I believe you shouldn't, as deprenyl (selegiline) is a MAOI (albeit safer than other MAOIs), but better be safe than sorry.

Lilienthal
(Moderator)
09-10-01 16:00
No 211913
      Re: BPAP, a catecholamine acticity enhancer

I run across that paper some weeks ago. If you read it carefully you will see that it doesn't fit any scientific standards.

I would call their activity data random numbers crazy . My favorite is the part where they are speculating that taking a few micrograms daily would increase your life span. SciFi at its best.

My opinion is that their compounds are just serotonine reuptake inhibitors. The structure activity relationship supports that.

Rhodium
(Chief Bee)
09-10-01 18:38
No 211914
User Picture       Re: BPAP, a catecholamine acticity enhancer

Which paper, the BPAP one, or the one concerning deprenyl?

Lilienthal
(Moderator)
09-10-01 18:57
No 211916
      Re: BPAP, a catecholamine acticity enhancer

The BPAP one

Rhodium
(Chief Bee)
09-10-04 14:47
No 530644
User Picture       Studies with endogenous enhancer substances

_{Review article}
Pharmacological studies with endogenous enhancer substances: β-phenylethylamine, tryptamine, and their synthetic derivatives
Seiichiro Shimazu and Ildikó Miklya, Progress in Neuro-Psychopharmacology and Biological Psychiatry 28(3), 421-427 (2004)

Abstract
The discovery of enhancer regulation in the mesencephalon and the concept that it plays a key role in the operation of innate and acquired drives [Neurochem. Res. 28 (2003) 1187] sets the trace amines (TAs) in their true physiological perspective. The regulation is defined as the existence of enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances. For the time being, only β-phenylethylamine (PEA) and tryptamine are the experimentally analyzed examples. (−)-Deprenyl (selegiline), widely used in Parkinson's disease and Alzheimer's disease today, and known as the first selective monoamine oxidase (MAO) type-B inhibitor for decades, was identified as a PEA-derived synthetic mesencephalic enhancer substance. An important and convincing confirmation of the enhancer concept was the recent development of a highly specific and potent tryptamine-derived synthetic mesencephalic enhancer substance, (−)-1-(benzofuran-2-yl)-2-propylaminopentane [(−)-BPAP]. This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease.

^{The Hive - Clandestine Chemists Without Borders}

scarmani
(Hive Bee)
09-11-04 09:05
No 530826
User Picture       More BPAP References
(Rated as: good read)

The reference posted by Quicksilver:

R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release.
Seiichiro Shimazu, Kazue Takahata, Hiroshi Katsuki, Hiroko Tsunekawa, Akie Tanigawa, Fumio Yoneda, Joseph Knoll, Akinori Akaike,
Eur J Pharmacol. 421(3), 181-189 (2001)

Transporter-mediated actions of R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane.
Seiichiro Shimazua, Hiroko Tsunekawaa, Fumio Yonedaa, Hiroshi Katsuki, Akinori Akaikeb, Aaron Janowsky,
Eur J Pharmacol. 482(1-3), 9-16 (2003)

Reading some papers by Joseph Knoll I agree, they feel like questionable science -- with homeopathic concentrations and unusual, eccentric theories about "drives" and "life-force". Despite this the data about BPAP still seem very interesting and suggest BPAP would be a stimulant.

boot from the shadow of a broken mirror

Fastandbulbous
(Hive Bee)
09-11-04 13:47
No 530843
User Picture       BPAP for depression

This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease.

If BPAP is that effective on dopaminergic systems in the CNS, I can't see it getting approval by the FDA. They forced other countries to stop using amineptine as a clinical antidepressant because it was too effective a dopamine re-uptake inhibitor, and as such had a mild abuse potential (with side effects like spontaneous orgasm, I imagine the FDA/DEA had a fit about it's clinical use!)

That is right, the Mascara Snake: Fast and bulbous

	https://the-hive.archive.erowid.org	the-hive@erowid.org



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	All 12 posts		Subject: BPAP, a catecholamine activity enhancer		Please login to post		Down


		Rhodium (Chief Bee) 09-09-01 15:25 No 211596				BPAP, a catecholamine activity enhancer
						This could be something interesting, a compound that increases the activity of catecholamines in the brain (like dopamine), but without being a stimulant itself. Could somebody more pharmacologically inclined than myself elaborate of the implications of such a substance? It seems to be easy to synthesise, too. Enantioselective synthesis and absolute configuration of (−)-1-(benzofuran-2-yl)-2-propylaminopentane, ((−)-BPAP), a highly potent and selective catecholaminergic activity enhancer Takahiro Oka, Takuya Yasusa, Takashi Ando, Mayumi Watanabe, Fumio Yoneda, Toshimasa Ishida and Joseph Knoll Bioorganic & Medicinal Chemistry 9(5), 1213-1219 (2001) (https://www.rhodium.ws/pdf/bpap.pdf) Abstract Enantioselective synthesis and absolute configuration of (−)-1-(benzofuran-2-yl)-2-propylaminopentane ((−)-BPAP), which is a highly potent and selective catecholaminergic activity enhancer (CAE) substance, are described. The synthetic approach consists of the coupling reaction of benzofuran with (R)-N-tosyl-2-propylazirizine or (R)-N-methoxy-N-methylnorvaliamide, followed by appropriate modifications of the resulting coupling products. As the results, (−)-BPAP turned out to have the R configuration, which was finally confirmed by X-ray crystallographic analysis.



		Quicksilver (Hive Bee) 09-09-01 17:11 No 211609				Re: BPAP, a catecholamine acticity enhancer
						More fun stuff to read... (-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release. Eur J Pharmacol 2001 Jun 15;421(3):181-189 Shimazu S, Takahata K, Katsuki H, Tsunekawa H, Tanigawa A, Yoneda F, Knoll J, Akaike A. Institute of Research and Development, Fujimoto Pharmaceutical Corporation, 1-3-40 Nishiotsuka, Osaka 580-8503, Matsubara, Japan. "Catecholaminergic and serotoninergic activity enhancer" effects are newly found mechanisms of action of a class of compound that enhance impulse propagation-mediated release of catecholamines and serotonin in the brain. In the present study, (-)-1-(benzofuran-2-yl)-2-propylaminopentane hydrochloride [(-)-BPAP HCl], a compound with selective and potent "catecholaminergic and serotoninergic activity enhancer" effects, was tested for its efficacy to potentiate locomotor activity in normal rats and to attenuate hypolocomotion in reserpine-treated rats. (-)-BPAP HCl potentiated locomotor activity in non-habituated rats during a 2-h observation period dose-dependently (0.3-10 mg/kg). (-)-BPAP HCl (1-3 mg/kg) was also effective to reverse reserpine-induced hypolocomotion. The effects of (-)-BPAP HCl in normal and reserpine-treated rats were attenuated by the dopamine D1 receptor antagonist, R( )-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390), suggesting that the effects of (-)-BPAP HCl were mediated by activation of the dopaminergic system. In addition, the administration of (-)-BPAP HCl increased ipsilateral turning in unilaterally 6-hydroxydopamine-lesioned rats, implying presynaptic activation of nigrostriatal dopaminergic terminals by (-)-BPAP HCl. Furthermore, although antiparkinsonian agents, such as apomorphine and amantadine, failed to improve reserpine-induced ptosis, (-)-BPAP HCl significantly improved ptosis. These findings suggested that a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release.



		Quicksilver (Hive Bee) 09-09-01 17:13 No 211610				Re: BPAP, a catecholamine acticity enhancer
						A more biological review... (J Knoll's work seems to be a good starting point to look into) (-)Deprenyl (Selegiline): past, present and future. Neurobiology (Bp) 2000;8(2):179-199 Knoll J. Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary. (-)Deprenyl (Selegiline), the N-propargyl analogue of (-)methamphetamine, is the only drug in clinical case which, by enhancing the impulse propagation mediated release of noradrenaline and dopamine in the brain (catecholaminergic activity enhancer, CAE, effect), keeps in small doses without side-effects the catecholaminergic brain system on a higher activity level. (-)Deprenyl stimulates the catecholaminergic neurons selectively in the brain because, in contrast to PEA and the amphetamines which induce the continuous release of noradrenaline and dopamine from their intraneuronal stores, (-)deprenyl is devoid of this property. It is due to the CAE effect that a) the maintenance of rats on (-)deprenyl during the postdevelopmental phase of their life slows the age-related decline of sexual and learning performances and prolongs life significantly; b) patients with early, untreated Parkinson's disease maintained on (-)deprenyl need levodopa significantly later than their placebo-treated peers, and when on levodopa plus (-)deprenyl, they live significantly longer than patients on levodopa alone; and c) in patients with moderately severe impairment from Alzheimer's disease, treatment with (-)deprenyl slows the progression of the disease. It is reasonable to expect that a prophylactic low dose administration of a safe catecholaminergic activity enhancer substance during the postdevelopmental phase of life will slow the age-related decline of behavioral performances, delay natural death and decrease susceptibility to Parkinson's disease and Alzheimer's disease.



		foxy2 (Distinctive Doe) 09-10-01 00:47 No 211720				Re: BPAP, a catecholamine acticity enhancer
						Dam it time to order the Deprenyl!!! Do Your Part To Win The War



		RacerX (Newbee) 09-10-01 04:06 No 211766				Re: BPAP, a catecholamine acticity enhancer
						I have the Selegiline (Beprynl) does this mean I should be mixing it with say a gram of yabba a day?



		Rhodium (Chief Bee) 09-10-01 11:05 No 211842				Re: BPAP, a catecholamine acticity enhancer
						I believe you shouldn't, as deprenyl (selegiline) is a MAOI (albeit safer than other MAOIs), but better be safe than sorry.



		Lilienthal (Moderator) 09-10-01 16:00 No 211913				Re: BPAP, a catecholamine acticity enhancer
						I run across that paper some weeks ago. If you read it carefully you will see that it doesn't fit any scientific standards. I would call their activity data random numbers . My favorite is the part where they are speculating that taking a few micrograms daily would increase your life span. SciFi at its best. My opinion is that their compounds are just serotonine reuptake inhibitors. The structure activity relationship supports that.



		Rhodium (Chief Bee) 09-10-01 18:38 No 211914				Re: BPAP, a catecholamine acticity enhancer
						Which paper, the BPAP one, or the one concerning deprenyl?



		Lilienthal (Moderator) 09-10-01 18:57 No 211916				Re: BPAP, a catecholamine acticity enhancer
						The BPAP one



		Rhodium (Chief Bee) 09-10-04 14:47 No 530644				Studies with endogenous enhancer substances
						_{Review article} Pharmacological studies with endogenous enhancer substances: β-phenylethylamine, tryptamine, and their synthetic derivatives Seiichiro Shimazu and Ildikó Miklya, Progress in Neuro-Psychopharmacology and Biological Psychiatry 28(3), 421-427 (2004) Abstract The discovery of enhancer regulation in the mesencephalon and the concept that it plays a key role in the operation of innate and acquired drives [Neurochem. Res. 28 (2003) 1187] sets the trace amines (TAs) in their true physiological perspective. The regulation is defined as the existence of enhancer-sensitive neurons in the brain capable of working in a split-second on a high activity level due to endogenous enhancer substances. For the time being, only β-phenylethylamine (PEA) and tryptamine are the experimentally analyzed examples. (−)-Deprenyl (selegiline), widely used in Parkinson's disease and Alzheimer's disease today, and known as the first selective monoamine oxidase (MAO) type-B inhibitor for decades, was identified as a PEA-derived synthetic mesencephalic enhancer substance. An important and convincing confirmation of the enhancer concept was the recent development of a highly specific and potent tryptamine-derived synthetic mesencephalic enhancer substance, (−)-1-(benzofuran-2-yl)-2-propylaminopentane [(−)-BPAP]. This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease. ^{The Hive - Clandestine Chemists Without Borders}



		scarmani (Hive Bee) 09-11-04 09:05 No 530826				More BPAP References (Rated as: good read)
						The reference posted by Quicksilver: R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane enhances locomotor activity in rats due to its ability to induce dopamine release. Seiichiro Shimazu, Kazue Takahata, Hiroshi Katsuki, Hiroko Tsunekawa, Akie Tanigawa, Fumio Yoneda, Joseph Knoll, Akinori Akaike, Eur J Pharmacol. 421(3), 181-189 (2001) Transporter-mediated actions of R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane. Seiichiro Shimazua, Hiroko Tsunekawaa, Fumio Yonedaa, Hiroshi Katsuki, Akinori Akaikeb, Aaron Janowsky, Eur J Pharmacol. 482(1-3), 9-16 (2003) Reading some papers by Joseph Knoll I agree, they feel like questionable science -- with homeopathic concentrations and unusual, eccentric theories about "drives" and "life-force". Despite this the data about BPAP still seem very interesting and suggest BPAP would be a stimulant. boot from the shadow of a broken mirror



		Fastandbulbous (Hive Bee) 09-11-04 13:47 No 530843				BPAP for depression
						This substance, which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson's disease, and Alzheimer's disease. If BPAP is that effective on dopaminergic systems in the CNS, I can't see it getting approval by the FDA. They forced other countries to stop using amineptine as a clinical antidepressant because it was too effective a dopamine re-uptake inhibitor, and as such had a mild abuse potential (with side effects like spontaneous orgasm, I imagine the FDA/DEA had a fit about it's clinical use!) That is right, the Mascara Snake: Fast and bulbous

All 12 posts	End of thread	Top