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Medicines

Picralima nitida

Category: Medicines

Type

Voluntary

Introduction and description

Introduction

Akuammine is the most abundant active alkaloid found in the seeds from the tree Picralima nitida, commonly known as Akuamma.  It is an opiate, but its action is principally on the  kappa opioid receptor, as such it is not a plant that gives you direct spiritual experience in the way that opium or morphine does.  But it heals and is useful as a means of healing as such it is worthwhile including it because it indirectly helps spiritual experience in the suppression category by relieving pain and illness.

The dried seeds from this plant are used in traditional medicine throughout West Africa, particularly in Ghana as well as in the Ivory Coast and Nigeria.  The seeds are crushed or powdered and taken orally.

In traditional African medicine, Picralima nitida seeds are used for the treatment of  malaria and diarrhoea.  It is used as a painkiller and for its antipyretic, anti-diabetic and anti-inflammatory effects.

The fruit pulp, possesses hypoglycaemic properties.

Akuammicine from the seeds has been demonstrated to ‘stimulate glucose uptake’ supporting the traditional use of the seeds of P. nitida in the management of diabetes mellitus in Nigeria.

An enterprising Ghanaian hospital started manufacturing standardised 250mg capsules of the powdered P. nitida seed, and sold them around the country where they became widely accepted as a safe and effective pain relief product. This then led researchers to try and discover the active component of the seeds.

The bark of  Picralima nitida can be soaked in boiling water and has been shown to be effective against Trypanosomiasis or trypanosomosis  -  a very nasty set of diseases caused by parasitic protozoan trypanosomes of the genus Trypanosoma. Approximately 500,000 men, women and children in 36 countries of sub-Saharan Africa suffer from human Africa trypanosomiasis. The other human form of trypanosomiasis, called Chagas disease, causes 21,000 deaths per year  mainly in Latin America 

Background

The alkaloids

The following lists the main alkaloids in the seeds of Picralima nitida.  One group of alkaloids – the Akuammine family are generally speaking opioids, but there is another group in the seeds  - the pericine group.  What we can see is that overall, in the Akuammine group any mu activity appears to be cancelled out, but the strongest activity comes from delta and particularly kappa receptors .  The pericine group are still a bit more of a mystery and it may be that the other health giving properties are obtained from them: 

  • Akuammidine - Akuammine is the main alkaloid found in the seeds, comprising 0.56% of the dried powder.  It is structurally related to both yohimbine and mitragynine [see kratom].  Akuammidine showed a preference for opioid binding sites with Ki values of 0.6, 2.4 and 8.6 microM at mu-, delta- and kappa-opioid binding sites, respectively.  This makes it essentially a kappa agonist with some delta and even less mu activity.  Akuammidine has hypotensive, skeletal muscle relaxant and local analgesic activities. Its local analgesic activity is about 3 times as potent as codeine. It acts selectively as a sympatholytic, unaccompanied by parasympatholytic effects. 
  • Akuammine - akuammine also showed high affinity for mu-opioid binding sites (Ki 0.5 microM) but was an antagonist at mu-opioid receptors with a pK(B) of 5.7 against the selective mu-opioid receptor agonist enkephalin (DAMGO).   Its other properties, however, suggest it has agonistic properties at other opioid sites.  Akuammine has strong sympathomimetic and local analgesic activities; its effects are comparable to that of cocaine. It causes marked and lasting hypotension in dogs, without affecting respiration. In higher doses it causes a strong inhibitory effect on intestinal peristaltic movements. At such doses it also has hypertensive activity with a weaker, but longer lasting effect than yohimbine. 
  • Akuammicine  - has the highest affinity for kappa-opioid binding sites (Ki 0.2 microM) and was a full agonist at kappa-opioid receptors in the guinea pig ileum preparation but a partial kappa-opioid receptor agonist in the vasa deferentia of the mouse and the rabbit 
  • Pseudoakuammigine - Pseudo-akuammigine exhibits both anti-inflammatory and analgesic actions.   As an analgesic, ?-akuammigine is 3.5 less potent than morphine. The ED50 values were Morphine (2.9 ?M), ?-akuammigine (10 ?M). Naloxone  significantly antagonises the analgesic action of the alkaloid by 35.8±6.8%. Naloxone is an antagonist with high affinity for ?-opioid receptors  and  a lower affinity, at ?- and ?-opioid receptors.  Thus what is known so far is that the analgesic actions are mediated via interaction with opioid receptors of some sort.  Pseudo-akuammigine acts as an indirect reversible and competitive parasympathomimetic. In low doses it excites and in high doses it inhibits the central nervous system, respiration, contraction of the skeletal muscles and contraction of the smooth muscles. It has local analgesic, anti-inflammatory, and hypotensive activities. 
  • Akuammigine showed little or no efficacy in one opioid bioassay. BUT it  shows clear sympatholytic activity and antagonizes the effect of adrenaline on the heart, vessels and regulatory centre of the circulation system.  So it may act on the adrenoceptors 
  • Pericine – pericine has been shown to bind to mu opioid receptors, and has an IC50 of 0.6?mol, around 6x more potent than codeine when tested in the same assay. However it may also have convulsant effects. 
  • Picraline – no more known 
  • Picraphylline – no more known 
  • Picracine – no more known 
  • Picranitine– no more known 
  • Burnamin /eburnamine (desacetylpicraline - no more known)
  • Desacetylakuammiline (rhazimol).

and a mixture of four 5-hydroxy tryptamine amides

None of the alkaloids has significant activity for opioid receptor-like binding sites (ORL1-binding sites) with Ki values >> 10 microM.

 A 250 mg "Picap Capsule" sold commercially contains about 1.4 mg of akuammine, plus 0.085 mg akuammidine and 0.015 mg  akuammigine.

Overall, the alkaloids possess varying degrees of agonist and antagonist activity at opioid receptors but possess neither high affinity nor selectivity for mu-, delta- or kappa-opioid receptors or the ORL1-receptor.

The anti-malarial activity has been demonstrated in the laboratory.  In vivo antiplasmodial activity of the seed extract of Picralima nitida when evaluated in Plasmodium berghei berghei infected mice showed significant (P<0.05) antiplasmodial activity, though not comparable to that of the standard drug, chloroquine.  Plasmodium berghei is a unicellular parasite (protozoan).  It is used as a  practical model organism in the laboratory for the experimental study of human malaria.

References and further reading

Opioid activity of alkaloids extracted from Picralima nitida (fam. Apocynaceae). - Menzies JR, Paterson SJ, Duwiejua M, Corbett AD; Department of Biological Sciences, Glasgow Caledonian University, UK.

Akuammine and dihydroakuammine, two indolomonoterpene alkaloids displaying affinity for opioid receptors.  - Lewin G, Le Ménez P, Rolland Y, Renouard A, Giesen-Crouse E. Journal of Natural Products. 1992 Mar

Akuammine: an antimalarial indolemonoterpene alkaloid of Picralima nitida seeds.  - Kapadia GJ, Angerhofer CK, Ansa-Asamoah R. Planta Medica. 1993 Dec.

Pseudo-akuammigine, an alkaloid from Picralima nitida seeds, has anti-inflammatory and analgesic actions in rats.  - Duwiejua M, Woode E, Obiri DD. Journal of Ethnopharmacology. 2002; (81):73-79.

Brine shrimp toxicity of some plants used as traditional medicines in Kagera Region, north western Tanzania. - Moshi MJ, Innocent E, Magadula JJ, Otieno DF, Weisheit A, Mbabazi PK, Nondo RS; Department of Biological and Preclinical Studies, Institute of Traditional Medicine, Muhimbili University of Health and Allied Sciences,  Dar es Salaam, Tanzania.

Alkaloids of Picralima nitida Stapf. V. Isolation of a new alkaloid: picraline - OLIVIER L, LEVY J LE MEN J  JANOT MM PMID: 14481845

Evaluation of antiplasmodial activity of ethanolic seed extract of Picralima nitida - Okokon JE, Antia BS, Igboasoiyi AC  Essien EE, Mbagwu HO; Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria.

Use of extracts of Picralima nitida bark in the treatment of experimental trypanosomiasis: a preliminary study - Wosu LO  Ibe CC; Department of Veterinary Medicine, University of Nigeria, Nsukka.

Detection of pericine, a new CNS-active indole alkaloid from Picralima nitida cell suspension culture by opiate receptor binding studies. - Arens H, Borbe HO, Ulbrich B, Stöckigt J PMID: 6298847

Detection of Pericine, a New CNS-active Indole Alkaloid from Picralima nitida Cell Suspension Culture by Opiate Receptor Binding Studies.  - Arens H, Borbe HO, Ulbrich B, Stöckigt J. Planta Medica. 1982 Dec;46(12):210-4. PMID 17396975

Glucose uptake stimulatory effect  of akuammicine from Picralima nitida (Apocynaceae)  - Hafsat Shitt,  Alexander Gray,  Brian Furman  and Louise Young; National Institute for Pharmaceutical Research and Development (NIPRD), Idu. Nigeria and Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow UK

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