1 COMPONDS AFFECTING PSYCHIC STATE Main effect is change of psychic state Effects of natural psychic state affecting compounds are known from ancient times – cult and religious ceremonies Division: • PSYCHOLEPTICS (central suppression) • PSYCHOANALEPTICS (central stimulation) • PSYCHODYSLEPTICS (hallucinogens, compounds triggering depersonalization) PSYCHOPHARMACS NEUROLEPTICS RESERPINUM – RESERPINE (ČL 2002) Source: Different Rauwolfia spp., mainly Rauwolfia serpentina – snakeroot or sarpagandha (Apocynaceae) Drug: Rauwolfiae radix Indol monoterpenic alkaloid of yohimbane type Obtain exclusivelly by isolation Dosage: 5 – 15 mg pro die 2 RESERPINUM – RESERPIN (ČL 2002) MeO N H N H H H3 COOC H OMe O CO OMe OMe OMe DEPENDENCE -- ADDICTION -- WHO Drug addiction is according to the WHO compulsion to intake of psychotropic active compound („drug“) for feeling of well being which causes. The insufficiency of this compound triggers symptoms of abstinence. Tendency to increase doses. Can be: • Somatic • Psychic • Combination It starts at people, which consume drugs continually or periodically. Addiction is triggered after repeated application of some therapeutics and rises the craving (not compulsion) for repeated application. • No tendency (or only small) to increase doses • Symptom of psychic, not somatic dependence • Do not rise abstinent symptoms 3 PSYCHODYSLEPTICS • Almost no therapeutic importance • Toxicological importance • Abuse as narcotics • Subjected to assignation about narcotic substances • Induce pleasant initial hallucinations • Induce dependence and can trigger latent psychosis • Abuse is generally dangerously rising PSYCHODYSLEPTICS • DERIVATIVES OF INDOL (psilocybine, bufotenine, ergine, semisynth. LSD) • PHENYLETHYLAMINE DERIVATIVES (meskaline) • CANNABIS CONTAIN COMPOUNDS (tetrahydrocannabinol – THC, marihuana, hashish) • ISOXAZOL DERIVATIVES (muscimol, ibotenic acid) • ANTICHOLINERGIC COMPOUNDS (scopolamine, atropine) 4 PSYCHODYSLEPTICS PSILOCYBINE Source: mushrooms Psilocybe, Conocybe, Stropharia spp. (Agaricaceae). Middle and South America „TEONANACATL“ The first in nature described phosphorylated indol derivative N,N-dimethyltryptamin-4- phosphate Effective dose = 4-8 mg Effect gets on after 30-60 min. Visual and acoustic hallucinations Typical imaginations of ability to fly Psylocin is a metabolite. N H O P O OH O N + CH3 CH3 H - 4 PSYCHODYSLEPTICS PSILOCYBIN Europe: Psilocybe semilanceata – liberty cap P. cyanescens – potent Psilocybe or wavy cap Psilocybine contain 0,01-2,5 %/dry weight, in average 1 % Effective dose in cca 0,5-1 g of dried fruiting bodies = cca 5-10 g of fresh mushrooms = cca 6-12 of fresh fruiting bodies 5 Effect of psilocybine on the spider webbing PSYCHODYSLEPTICS BUFOTENINE Source: Piptadenia peregrina (snuff powder from seeds) Amanita citrina, A. porphyria (mushrooms) Bufo vulgaris N,N-dimethyl-5-hydroxytryptamin 10-15 mg • short-termed hallucinations, anxiety • time-space distortions • depersonalization • macropsia N H N CH3 CH3 OH 5 6 BUFOTENIN AND CHEMOSYSTEMATICS STRUCTURAL SIMILARITY Melatonin – produced in epiphysis (pineal gland) • sets up and synchronizes biologic clock, supports circadian system • increases quality of sleep and fall asleep • Informs about year period, affects animal reproduction • Supports immune system, scavenges free radicals, possess anticancerogenic, antigonadotropic effects, slowers aging Serotonin – tissue hormone found especially in thrombocytes • neurotransmitter in brain and peripheral tissues, in CNS – mood, cognitive functions, sensoric perception, pain perception, sexual behavior • Triggers smooth muscles contraction N CH2 -CH2 -NH-CO-CH3 MeO 3 5 Melatonin N OH NH2 Serotonin 7 IPOMOEA VIOLACEA PSYCHODYSLEPTICS ERGIN (amide of lysergic acid) Source: Seeds of Ipomoea violacea – morning glory, Beach Moonflower Rivea corymbosa syn. Turbina corymbosa Christmas vine (Convolvulaceae) 2-10 mg – depersonalization Used by Aztecs – (tlililzin, ololiuqui) for religious ceremonies N N H CH3 H CONH2 8 PSYCHODYSLEPTICS LSD (diethylamide of lysergic acid) Semisyntetic derivative Previously uterotonic Effect elucidate accidentally in 1943 by A. Hofmann Misused hallucinogen Effective dose 20-25 μg (0,000020-0,000025 g) Initiates chromosome aberrations Prof. Timothy Leary - Harvard N N H CH3 H CO N C2 H5 C2 H5 PSYCHODYSLEPTICS MESKALINE Synonyms: Peyotl, Mescal buttons (for smoking and chewing) Source: Echinocactus williamsii = Lopophora Lewinii, Trichocereus Transversely cut slices – drying – mescal „buttons“ 9 PSYCHODYSLEPTICS MESKALINE Effective compounds: 3,4,5-trimethoxy-β-fenylethylamine In cactuses 5-7 % 0,2-0,6 g of mescaline triggers hallucinations OMe OMeMeO CH2 CH2 NH2 PHENYLETHYLAMINE DERIVATIVES OH OH CH-OH CH2 NH-CH3 CH-OH CH-CH3 NH-CH3 CH2 CH-CH3 NH2 CH2 CH-CH3 NH-CH3 CH2 CH-CH3 NH-CH3 O O Epinephrine Ephedrine Amphetamine Pervitine Ecstasy (MDMA) 10 PSYCHODYSLEPTICS ISOXAZOLES Source: Amanita pantherina – Panther cap Amanita muscaria – fly amanita • Pulp pure white color and poisonous PSYCHODYSLEPTICS ISOXAZOLS Contain mixture of isoxazol alkaloids Together with muscarine affect parasympaticus. Muscimolincreases salivation, sweting, secretion of bile, pancreatic secretion, evoke psychic exaltation, intoxicating euphoria. Initiate state similar to alcohol intoxication - swoon, hallucination, fury Used to trigger state of berserc. O NC H2 O N + H H H O NC H OH COOH NH2 muscimol ibotenic acid 11 PSYCHODYSLEPTICS MARIHUANA, HASHISH, THC Source: Cannabis indica – indian hemp (Cannabaceae) Flowering tops of female plants Absorbed by mucosa of respiratory or digestive tract Mostly often used for smoking Hashish – resin obtained from leaves and flowers Contain cannabinoids, effective THC PSYCHODYSLEPTICS MARIHUANA, HASHISH, THC O CH3 OH H H CH3CH3 9-tetrahydrocannabinol 1 9 antiemetic dronabinol (MARINOL) affects tremor and diskinesis at Parkinson disease 12 Effects of some hemp resin components Effect Compound antibiotic sedative analgesic narcotic Canabidiol + - - Canabidiolic acid + + - Canabinol - - - Canabigerol + - - Canabigerolic acid + - - Canabichromen - + - THC - - - + 13 ANTIPARKINSONICS Parkinson disease – presenile hereditary-degenerative illness, intellect not touched Decrease of dopamine and serotonin level in bazal ganglia Elevated tonus of central cholinergic system Affects extra pyramidal motile system, loss of associated and automatic movements, tremor For symptoms suppression it is possible to use central anticholinergic compounds (parasympatolytics) ANTIPARKINSONICS TROPANE ALKALOIDS N CH3 O H CO C CH2OH H N CH3 O H CO C CH2OH H O C=O T C=O T (-)-S-hyoscyamine (-)-S-scopolamine 3 6 7 belladonine (T = tropyl-) (dimer of apoatropine)